                         SEQUENCE LISTING

<110>  The Trustees of The University of Pennsylvania
 
<120>  COMPOSITIONS USEFUL FOR TREATMENT OF CHARCOT-MARIE-TOOTH DISEASE

<130>  UPN-20-9141.PCT

<150>  US 63/051,336
<151>  2020-07-13

<150>  US 63/173,045
<151>  2021-04-09

<160>  90    

<170>  PatentIn version 3.5

<210>  1
<211>  4585
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector Genome Syn.PI.hMfn2opt.link.hMfn2 miR1693.WPRE.bGH


<220>
<221>  repeat_region
<222>  (1)..(141)
<223>  5'ITR

<220>
<221>  promoter
<222>  (223)..(682)
<223>  hSynapsin

<220>
<221>  Intron
<222>  (694)..(826)
<223>  Promega Chimeric Intron

<220>
<221>  misc_signal
<222>  (857)..(862)
<223>  Kozak

<220>
<221>  CDS
<222>  (863)..(3136)
<223>  human Mfn2 engineered

<220>
<221>  misc_feature
<222>  (3134)..(3139)
<223>  Dbl stop codon

<220>
<221>  misc_feature
<222>  (3140)..(3229)
<223>  linker

<220>
<221>  misc_binding
<222>  (3230)..(3252)
<223>  5'flank

<220>
<221>  misc_feature
<222>  (3253)..(3316)
<223>  hMfn2 miR1693

<220>
<221>  misc_binding
<222>  (3317)..(3360)
<223>  3'flank

<220>
<221>  misc_feature
<222>  (3463)..(4045)
<223>  WRPE

<220>
<221>  misc_feature
<222>  (4410)..(4455)
<223>  Additional AAV squences

<220>
<221>  repeat_region
<222>  (4456)..(4585)
<223>  3'ITR

<400>  1
ccttaattag gctgcgcgct cgctcgctca ctgaggccgg gcgaccaaag gtcgcccgac       60

gcccgggctt tgcccgggcg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacgt      180

agccatgctc taggaagatc ggaattcgcc cttaagctag actcgagctg cagagggccc      240

tgcgtatgag tgcaagtggg ttttaggacc aggatgaggc ggggtggggg tgcctacctg      300

acgaccgacc ccgacccact ggacaagcac ccaaccccca ttccccaaat tgcgcatccc      360

ctatcagaga gggggagggg aaacaggatg cggcgaggcg cgtgcgcact gccagcttca      420

gcaccgcgga cagtgccttc gcccccgcct ggcggcgcgc gccaccgccg cctcagcact      480

gaaggcgcgc tgacgtcact cgccggtccc ccgcaaactc cccttcccgg ccaccttggt      540

cgcgtccgcg ccgccgccgg cccagccgga ccgcaccacg cgaggcgcga gatagggggg      600

cacgggcgcg accatctgcg ctgcggcgcc ggcgactcag cgctgcctca gtctgcggtg      660

ggcagcggag gagtcgtgtc gtgcctgaga gcggtaagta tcaaggttac aagacaggtt      720

taaggagacc aatagaaact gggcttgtcg agacagagaa gactcttgcg tttctgatag      780

gcacctattg gtcttactga catccacttt gcctttctct ccacagtacg tagaattcac      840

gcgtgctagc accggtgcca cc atg agc ctg ctg ttc agc cgg tgc aac agc       892
                         Met Ser Leu Leu Phe Ser Arg Cys Asn Ser          
                         1               5                   10           

atc gtg acc gtg aag aaa aac aag cgg cac atg gcc gaa gtg aac gcc        940
Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn Ala           
                15                  20                  25                

tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac ggc atc        988
Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile           
            30                  35                  40                    

ttc gag cag ctg ggc gcc tac atc caa gag agc gcc acc ttc ctg gaa       1036
Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu           
        45                  50                  55                        

gat acc tac aga aac gcc gag ctg gac ccc gtg acc aca gag gaa cag       1084
Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu Gln           
    60                  65                  70                            

gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg ggc atc tct gaa       1132
Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu           
75                  80                  85                  90            

gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc ggc cgg acc agc       1180
Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser           
                95                  100                 105               

aac ggc aag agc acc gtg atc aat gcc atg ctg tgg gac aaa gtg ctg       1228
Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu           
            110                 115                 120                   

ccc tct gga atc ggc cac acc acc aac tgc ttt ctg aga gtg gaa ggc       1276
Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu Gly           
        125                 130                 135                       

acc gac ggc cac gag gca ttt ctg ctg aca gag ggc tcc gag gaa aag       1324
Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys           
    140                 145                 150                           

cgg agc gcc aag aca gtg aac cag ctg gcc cat gct ctg cac cag gat       1372
Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp           
155                 160                 165                 170           

aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg tgg ccc aat agc       1420
Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser           
                175                 180                 185               

aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gat agc ccc ggg       1468
Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly           
            190                 195                 200                   

atc gat gtg acc acc gaa ctg gac agc tgg atc gac aag ttc tgc ctg       1516
Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu           
        205                 210                 215                       

gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag agc acc ctg atg       1564
Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met           
    220                 225                 230                           

cag acc gag aag cac ttt ttc cac aag gtg tcc gag cgg ctg agc aga       1612
Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg           
235                 240                 245                 250           

ccc aat atc ttt atc ctg aac aac aga tgg gac gcc agc gcc agc gag       1660
Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu           
                255                 260                 265               

ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg gaa cgg tgc aca       1708
Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr           
            270                 275                 280                   

tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga tct cag gcc ggc       1756
Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala Gly           
        285                 290                 295                       

gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg aac gcc cgg att       1804
Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg Ile           
    300                 305                 310                           

cag aaa gcc cag gga atg cct gaa ggc gga ggt gca ctg gcc gag gga       1852
Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly           
315                 320                 325                 330           

ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc gag       1900
Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu           
                335                 340                 345               

gag tgc atc agc cag agc gcc gtc aag acc aag ttc gag cag cat acc       1948
Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr           
            350                 355                 360                   

gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg atc atg gac agc       1996
Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser           
        365                 370                 375                       

ctg cat atg gcc gcc aga gag cag cag gtc tac tgc gag gaa atg cgg       2044
Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met Arg           
    380                 385                 390                           

gaa gag aga cag gac cgg ctg aag ttc atc gac aag cag ctg gaa ctg       2092
Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu           
395                 400                 405                 410           

ctg gcc cag gac tac aag ctg cgg atc aag cag atc acc gaa gag gtg       2140
Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu Val           
                415                 420                 425               

gaa aga cag gtg tcc acc gct atg gcc gag gaa atc aga cgg ctg agc       2188
Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser           
            430                 435                 440                   

gtg ctg gtc gac gac tac cag atg gac ttt cac ccc tct cca gtg gtg       2236
Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val Val           
        445                 450                 455                       

ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc gag gaa ggc ctg       2284
Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu           
    460                 465                 470                           

ggc aga aac atg agc gac aga tgc agc acc gcc atc acc aat agc ctg       2332
Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu           
475                 480                 485                 490           

cag acc atg cag cag gac atg atc gac ggc ctg aaa cct ctg ctg cct       2380
Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro           
                495                 500                 505               

gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc cgg cag tgc ttt       2428
Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe           
            510                 515                 520                   

agc ctg aac tac gac ctg aac tgc gac aag ctg tgc gcc gat ttc caa       2476
Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln           
        525                 530                 535                       

gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc aac       2524
Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn           
    540                 545                 550                           

aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg atg ggc tac aac       2572
Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn           
555                 560                 565                 570           

gat cag gtg cag agg ccc att cct ctg aca ccc gcc aat cct agc atg       2620
Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser Met           
                575                 580                 585               

cct cca ctg cct cag ggc agc ctg aca caa gag gaa ttc atg gtg tct       2668
Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val Ser           
            590                 595                 600                   

atg gtc acc ggc ctg gcc agc ctg acc agc aga aca tct atg ggc atc       2716
Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile           
        605                 610                 615                       

ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc tgg cgg ctg atc       2764
Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile           
    620                 625                 630                           

gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg tac gag aga ctg       2812
Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu           
635                 640                 645                 650           

acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag cgg cag ttt gtg       2860
Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val           
                655                 660                 665               

gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc tac acc ggc agc       2908
Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser           
            670                 675                 680                   

aat tgc agc cac cag gtg cag caa gag ctg tcc gga aca ttc gcc cac       2956
Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His           
        685                 690                 695                       

ctg tgt cag cag gtc gac gtg acc aga gag aac ctg gaa caa gag atc       3004
Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu Ile           
    700                 705                 710                           

gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc ctg cag agc aag       3052
Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser Lys           
715                 720                 725                 730           

gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac agc gag ctg aat       3100
Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn           
                735                 740                 745               

atg ttc acc cac cag tac ctg cag cct agc cgc taa taatgtacaa            3146
Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg                               
            750                 755                                       

gtaaagcgcc cgcaggcttg cacccgtacc tttgggagcg cgcgccctcg tcgtgtcgtg     3206

acgtcacccg ttctgttgga tccctggagg cttgctgaag gctgtatgct gttcttataa     3266

accttgagga ctgttttggc cactgactga cagtcctcag tttataagaa caggacacaa     3326

ggcctgttac tagcactcac atggaacaaa tggcccagat ctagggtggg gccacctgcc     3386

ggtaggtgtg cggtaggctt ttctccgtcg caggacgcag ggttcgggcc tagcttaagc     3446

ttctcgagat cgataatcaa cctctggatt acaaaatttg tgaaagattg actggtattc     3506

ttaactatgt tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg     3566

ctattgcttc ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc     3626

tttatgagga gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg     3686

acgcaacccc cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg     3746

ctttccccct ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga     3806

caggggctcg gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct     3866

ttccttggct gctcgcctgt gttgccacct ggattctgcg cgggacgccc ttctgctacg     3926

tcccttcggc cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc     3986

ctcttccgcg tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc     4046

cgcctgctga tcgccctgag cctggccctg gtgaccaaca gccaggtgca attgctagag     4106

tcgactctag agcggccgcc taaggctcga ctagagctcg ctgatcagcc tcgactgtgc     4166

cttctagttg ccagccatct gttgtttgcc cctcccccgt gccttccttg accctggaag     4226

gtgccactcc cactgtcctt tcctaataaa atgaggaaat tgcatcgcat tgtctgagta     4286

ggtgtcattc tattctgggg ggtggggtgg ggcaggacag caagggggag gattgggaag     4346

acaatagcag gcatgctggg gactcgagtt aagggcgaat tcccgataag gatcttccta     4406

gagcatggct acgtagataa gtagcatggc gggttaatca ttaactacaa ggaaccccta     4466

gtgatggagt tggccactcc ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca     4526

aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg agcgcgcag      4585


<210>  2
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  2

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  3
<211>  4560
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector Genome Syn.PI.rMnf2opt.link.rMfn2 miR1518 WPRE.BGH


<220>
<221>  repeat_region
<222>  (1)..(141)
<223>  5'ITR

<220>
<221>  promoter
<222>  (223)..(682)
<223>  hSynapsin

<220>
<221>  Intron
<222>  (694)..(826)
<223>  Promega Chimeric Intron

<220>
<221>  CDS
<222>  (863)..(3133)
<223>  rMfn2 engineered

<220>
<221>  misc_feature
<222>  (3134)..(3139)
<223>  Dbl stop codon

<220>
<221>  misc_feature
<222>  (3140)..(3229)
<223>  linker

<220>
<221>  misc_signal
<222>  (3230)..(3252)
<223>  5'flank

<220>
<221>  misc_feature
<222>  (3253)..(3316)
<223>  rMfn2 miR1518

<220>
<221>  misc_signal
<222>  (3317)..(3360)
<223>  3'flank

<220>
<221>  enhancer
<222>  (3457)..(4044)
<223>  WRPE

<220>
<221>  misc_feature
<222>  (4385)..(4430)
<223>  Additional AAV sequences

<220>
<221>  repeat_region
<222>  (4431)..(4560)
<223>  3'ITR

<400>  3
ccttaattag gctgcgcgct cgctcgctca ctgaggccgg gcgaccaaag gtcgcccgac       60

gcccgggctt tgcccgggcg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacgt      180

agccatgctc taggaagatc ggaattcgcc cttaagctag actcgagctg cagagggccc      240

tgcgtatgag tgcaagtggg ttttaggacc aggatgaggc ggggtggggg tgcctacctg      300

acgaccgacc ccgacccact ggacaagcac ccaaccccca ttccccaaat tgcgcatccc      360

ctatcagaga gggggagggg aaacaggatg cggcgaggcg cgtgcgcact gccagcttca      420

gcaccgcgga cagtgccttc gcccccgcct ggcggcgcgc gccaccgccg cctcagcact      480

gaaggcgcgc tgacgtcact cgccggtccc ccgcaaactc cccttcccgg ccaccttggt      540

cgcgtccgcg ccgccgccgg cccagccgga ccgcaccacg cgaggcgcga gatagggggg      600

cacgggcgcg accatctgcg ctgcggcgcc ggcgactcag cgctgcctca gtctgcggtg      660

ggcagcggag gagtcgtgtc gtgcctgaga gcggtaagta tcaaggttac aagacaggtt      720

taaggagacc aatagaaact gggcttgtcg agacagagaa gactcttgcg tttctgatag      780

gcacctattg gtcttactga catccacttt gcctttctct ccacagtacg tagaattcac      840

gcgtgctagc accggtgcca cc atg tct ctg ctg ttc agc cgg tgc aac agc       892
                         Met Ser Leu Leu Phe Ser Arg Cys Asn Ser          
                         1               5                   10           

atc gtg acc gtg aag aaa gac aag agg cac atg gcc gaa gtg aac gcc        940
Ile Val Thr Val Lys Lys Asp Lys Arg His Met Ala Glu Val Asn Ala           
                15                  20                  25                

tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac ggc atc        988
Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile           
            30                  35                  40                    

ttc gag cag ctg ggc gcc tac atc caa gag tct gcc ggc ttc ctg gaa       1036
Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Gly Phe Leu Glu           
        45                  50                  55                        

gat acc cac aga aac acc gag ctg gac ccc gtg acc aca gag gaa cag       1084
Asp Thr His Arg Asn Thr Glu Leu Asp Pro Val Thr Thr Glu Glu Gln           
    60                  65                  70                            

gtg ctg gac gtg aag ggc tac ctg tct aaa gtg cgg ggc atc agc gag       1132
Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu           
75                  80                  85                  90            

gtg ctg gct aga agg cat atg aag gtg gcc ttt ttc ggc agg acc agc       1180
Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser           
                95                  100                 105               

aac ggc aag agc acc gtg atc aac gcc atg ctg tgg gac aaa gtg ctg       1228
Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu           
            110                 115                 120                   

cct tct ggc atc ggc cac acc acc aac tgc ttt ctg aga gtc ggc ggc       1276
Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Gly Gly           
        125                 130                 135                       

aca gac ggc cac gag gct ttt ttg ctg acc gag ggc tcc gaa gag aag       1324
Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys           
    140                 145                 150                           

aaa tcc gtg aaa acc gtg aac cag ctg gcc cac gct ctg cac cag gat       1372
Lys Ser Val Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp           
155                 160                 165                 170           

gaa caa ctg cac gcc gga agc ctg gtg tcc gtg atg tgg cct aac agc       1420
Glu Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser           
                175                 180                 185               

aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gac tct cct gga       1468
Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly           
            190                 195                 200                   

atc gac gtg acc act gag ctg gac agc tgg atc gac aag ttc tgc ctg       1516
Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu           
        205                 210                 215                       

gac gcc gac gtg ttc gtg ctg gtg gct aac tct gag agc acc ctg atg       1564
Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met           
    220                 225                 230                           

cag acc gag aag cag ttc ttc cac aag gtg tcc gag agg ctg agc agg       1612
Gln Thr Glu Lys Gln Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg           
235                 240                 245                 250           

ccc aat atc ttt atc ctg aac aac aga tgg gac gcc agc gcc agc gag       1660
Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu           
                255                 260                 265               

ccc gag tat atg gaa gaa gtg cgg agg cag cat atg gaa agg tgt acc       1708
Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr           
            270                 275                 280                   

agc ttc ctg gtg gac gag ctg gga gtc gtg gat aga gca cag gcc ggc       1756
Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ala Gln Ala Gly           
        285                 290                 295                       

gac aga atc ttc ttc gtg tct gcc aaa gag gtg ctg agc gcc agg gtg       1804
Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Ser Ala Arg Val           
    300                 305                 310                           

cag aaa gcc cag gga atg cct gaa ggc ggc gga gct ttg gcc gag gga       1852
Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly           
315                 320                 325                 330           

ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc gag       1900
Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu           
                335                 340                 345               

gaa tgc atc agc cag agc gcc gtc aag aca aag ttc gag cag cac aca       1948
Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr           
            350                 355                 360                   

gtg cgg gcc aag cag atc gct gag gct gtg cgg ctg atc atg gac agc       1996
Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser           
        365                 370                 375                       

ctg cat atc gcc gct caa gag cag agg gtg tac tgc ctg gaa atg cgg       2044
Leu His Ile Ala Ala Gln Glu Gln Arg Val Tyr Cys Leu Glu Met Arg           
    380                 385                 390                           

gaa gag agg cag gac agg ctg aga ttc atc gac aag cag ctg gaa ctg       2092
Glu Glu Arg Gln Asp Arg Leu Arg Phe Ile Asp Lys Gln Leu Glu Leu           
395                 400                 405                 410           

ctg gcc cag gac tac aag ctg agg atc aag cag atg acc gaa gag gtg       2140
Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Met Thr Glu Glu Val           
                415                 420                 425               

gaa aga cag gtg tcc acc gcc atg gcc gag gaa atc cgt aga ctg tct       2188
Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser           
            430                 435                 440                   

gtg ctg gtc gac gag tac cag atg gac ttt cac ccc tct cca gtg gtg       2236
Val Leu Val Asp Glu Tyr Gln Met Asp Phe His Pro Ser Pro Val Val           
        445                 450                 455                       

ctg aag gtc tac aaa aac gag ctg cac agg cac atc gag gaa ggc ctg       2284
Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu           
    460                 465                 470                           

ggc aga aac atg agc gac agg tgc tct acc gct atc gcc agc agc ctg       2332
Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Ala Ser Ser Leu           
475                 480                 485                 490           

cag aca atg cag cag gac atg atc gac ggc ctg aag cct ctg ctg cct       2380
Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro           
                495                 500                 505               

gtg tct gtg cgg aac cag atc gat atg ctg gtg ccc agg cag tgc ttc       2428
Val Ser Val Arg Asn Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe           
            510                 515                 520                   

tcc ctg tcc tac gac ctg aac tgc gac aag ctg tgt gcc gac ttc caa       2476
Ser Leu Ser Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln           
        525                 530                 535                       

gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc aac       2524
Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn           
    540                 545                 550                           

aga ttc ctg gga cct aag aac tcc aga cgg gcc ctg ctg gga tac aac       2572
Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Leu Gly Tyr Asn           
555                 560                 565                 570           

gat cag gtg caa agg ccc ctg cct ctg aca cca gct aac cct tct atg       2620
Asp Gln Val Gln Arg Pro Leu Pro Leu Thr Pro Ala Asn Pro Ser Met           
                575                 580                 585               

cct cct ctg cct caa ggc tct ctg acc caa gag gaa ctg atg gtg tcc       2668
Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Leu Met Val Ser           
            590                 595                 600                   

atg gtc aca ggc ctg gct tcc ctg acc agc aga acc tct atg ggc atc       2716
Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile           
        605                 610                 615                       

ctg gtc gtc ggc gga gtt gtg tgg aaa gct gtt ggc tgg cgc ctg atc       2764
Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile           
    620                 625                 630                           

gcc ctg agc ttt gga ctg tac gga ctg ctg tac gtg tac gag aga ctg       2812
Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu           
635                 640                 645                 650           

acc tgg acc acc agg gcc aaa gag agg gcc ttc aag agg cag ttc gtg       2860
Thr Trp Thr Thr Arg Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val           
                655                 660                 665               

gaa tac gcc tcc gag aaa ctg cag ctg att atc tcc tac acc ggc agc       2908
Glu Tyr Ala Ser Glu Lys Leu Gln Leu Ile Ile Ser Tyr Thr Gly Ser           
            670                 675                 680                   

aac tgc agc cac cag gtg cag caa gag ctg tct gga aca ttc gcc cac       2956
Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His           
        685                 690                 695                       

ctg tgc cag cag gtc gac atc acc aga gac aac ctg gaa caa gag atc       3004
Leu Cys Gln Gln Val Asp Ile Thr Arg Asp Asn Leu Glu Gln Glu Ile           
    700                 705                 710                           

gcc gct atg aat aag aag gtg gaa gcc ctg gac tcc ctg cag agc aag       3052
Ala Ala Met Asn Lys Lys Val Glu Ala Leu Asp Ser Leu Gln Ser Lys           
715                 720                 725                 730           

gct aag ctg ctg aga aac aag gcc ggc tgg ctg gac tcc gag ctg aat       3100
Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn           
                735                 740                 745               

atg ttt atc cac cag tac ctg cag cct agc cgc tgatgatgta caagtaaagc     3153
Met Phe Ile His Gln Tyr Leu Gln Pro Ser Arg                               
            750                 755                                       

ggccgcaagc ttgcacccgt acctttggga gcgcgcgccc tcgtcgtgtc gtgacgtcac     3213

ccgttctgtt ggatccctgg aggcttgctg aaggctgtat gctgttctta taaaccttga     3273

ggacagtttt ggccactgac tgactgtcct cagtttataa gaacaggaca caaggcctgt     3333

tactagcact cacatggaac aaatggccca gatctagggt ggggccacct gccggtaggt     3393

gtgcggtagg cttttctccg tcgcaggacg cagggttcgg gcctagcttc tcgagatcga     3453

taatcaacct ctggattaca aaatttgtga aagattgact ggtattctta actatgttgc     3513

tccttttacg ctatgtggat acgctgcttt aatgcctttg tatcatgcta ttgcttcccg     3573

tatggctttc attttctcct ccttgtataa atcctggttg ctgtctcttt atgaggagtt     3633

gtggcccgtt gtcaggcaac gtggcgtggt gtgcactgtg tttgctgacg caacccccac     3693

tggttggggc attgccacca cctgtcagct cctttccggg actttcgctt tccccctccc     3753

tattgccacg gcggaactca tcgccgcctg ccttgcccgc tgctggacag gggctcggct     3813

gttgggcact gacaattccg tggtgttgtc ggggaaatca tcgtcctttc cttggctgct     3873

cgcctgtgtt gccacctgga ttctgcgcgg gacgcccttc tgctacgtcc cttcggccct     3933

caatccagcg gaccttcctt cccgcggcct gctgccggct ctgcggcctc ttccgcgtct     3993

tcgccttcgc cctcagacga gtcggatctc cctttgggcc gcctccccgc ctgctgatcg     4053

ccctgagcct ggccctggtg accaacagcc aggtgcaatt gaagctttct agagtcgact     4113

agagctcgct gatcagcctc gactgtgcct tctagttgcc agccatctgt tgtttgcccc     4173

tcccccgtgc cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat     4233

gaggaaattg catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg     4293

caggacagca agggggagga ttgggaagac aatagcaggc atgctgggga ctcgagttaa     4353

gggcgaattc ccgataagga tcttcctaga gcatggctac gtagataagt agcatggcgg     4413

gttaatcatt aactacaagg aacccctagt gatggagttg gccactccct ctctgcgcgc     4473

tcgctcgctc actgaggccg ggcgaccaaa ggtcgcccga cgcccgggct ttgcccgggc     4533

ggcctcagtg agcgagcgag cgcgcag                                         4560


<210>  4
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  4

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asp Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Gly Phe Leu Glu Asp Thr His Arg Asn Thr 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Gly Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Lys Ser Val Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Glu Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys Gln Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ala Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Ser Ala Arg Val Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Ile Ala Ala Gln 
    370                 375                 380                 


Glu Gln Arg Val Tyr Cys Leu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Arg Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Met Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Glu Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Ala Ser Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Asn Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Ser Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Leu Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Leu Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Leu Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Arg Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu Tyr Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Ile Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Ile Thr Arg Asp Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Val Glu Ala Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Ile His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  5
<211>  141
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' ITR

<400>  5
ccttaattag gctgcgcgct cgctcgctca ctgaggccgg gcgaccaaag gtcgcccgac       60

gcccgggctt tgcccgggcg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc t                                                141


<210>  6
<211>  460
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hSynapsin promoter

<400>  6
tcgagctgca gagggccctg cgtatgagtg caagtgggtt ttaggaccag gatgaggcgg       60

ggtgggggtg cctacctgac gaccgacccc gacccactgg acaagcaccc aacccccatt      120

ccccaaattg cgcatcccct atcagagagg gggaggggaa acaggatgcg gcgaggcgcg      180

tgcgcactgc cagcttcagc accgcggaca gtgccttcgc ccccgcctgg cggcgcgcgc      240

caccgccgcc tcagcactga aggcgcgctg acgtcactcg ccggtccccc gcaaactccc      300

cttcccggcc accttggtcg cgtccgcgcc gccgccggcc cagccggacc gcaccacgcg      360

aggcgcgaga taggggggca cgggcgcgac catctgcgct gcggcgccgg cgactcagcg      420

ctgcctcagt ctgcggtggg cagcggagga gtcgtgtcgt                            460


<210>  7
<211>  133
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Promega Chimeric Intron

<400>  7
gtaagtatca aggttacaag acaggtttaa ggagaccaat agaaactggg cttgtcgaga       60

cagagaagac tcttgcgttt ctgataggca cctattggtc ttactgacat ccactttgcc      120

tttctctcca cag                                                         133


<210>  8
<211>  583
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  WPRE

<400>  8
tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact atgttgctcc       60

ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg cttcccgtat      120

ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg aggagttgtg      180

gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa cccccactgg      240

ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc ccctccctat      300

tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg ctcggctgtt      360

gggcactgac aattccgtgg tgttgtcggg gaaatcatcg tcctttcctt ggctgctcgc      420

ctgtgttgcc acctggattc tgcgcgggac gcccttctgc tacgtccctt cggccctcaa      480

tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc cgcgtcttcg      540

ccttcgccct cagacgagtc ggatctccct ttgggccgcc tcc                        583


<210>  9
<211>  46
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  additonal AAV sequences

<400>  9
catggctacg tagataagta gcatggcggg ttaatcatta actaca                      46


<210>  10
<211>  130
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' ITR

<400>  10
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag                                                             130


<210>  11
<211>  2274
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  human Mfn2 engineered nucleic acid seuquence encoding mitofusin 2
       protein

<400>  11
atgagcctgc tgttcagccg gtgcaacagc atcgtgaccg tgaagaaaaa caagcggcac       60

atggccgaag tgaacgcctc tccactgaag cacttcgtga ccgccaagaa gaagatcaac      120

ggcatcttcg agcagctggg cgcctacatc caagagagcg ccaccttcct ggaagatacc      180

tacagaaacg ccgagctgga ccccgtgacc acagaggaac aggtgctgga tgtgaagggc      240

tacctgagca aagtgcgggg catctctgaa gtgctggcca gacggcatat gaaggtggcc      300

tttttcggcc ggaccagcaa cggcaagagc accgtgatca atgccatgct gtgggacaaa      360

gtgctgccct ctggaatcgg ccacaccacc aactgctttc tgagagtgga aggcaccgac      420

ggccacgagg catttctgct gacagagggc tccgaggaaa agcggagcgc caagacagtg      480

aaccagctgg cccatgctct gcaccaggat aagcagctgc atgccggaag cctggtgtcc      540

gtgatgtggc ccaatagcaa gtgccctctg ctgaaggacg acctggtgct gatggatagc      600

cccgggatcg atgtgaccac cgaactggac agctggatcg acaagttctg cctggacgcc      660

gacgtgttcg tgctggtggc caatagcgag agcaccctga tgcagaccga gaagcacttt      720

ttccacaagg tgtccgagcg gctgagcaga cccaatatct ttatcctgaa caacagatgg      780

gacgccagcg ccagcgagcc cgagtatatg gaagaagtgc ggcggcagca tatggaacgg      840

tgcacatcct ttctggtgga cgagctgggc gtcgtggata gatctcaggc cggcgacaga      900

atcttctttg tgtccgccaa agaggtgctg aacgcccgga ttcagaaagc ccagggaatg      960

cctgaaggcg gaggtgcact ggccgaggga tttcaagtgc ggatgttcga gttccagaac     1020

ttcgagcgga gattcgagga gtgcatcagc cagagcgccg tcaagaccaa gttcgagcag     1080

cataccgtgc gggccaagca gattgccgaa gccgtcagac tgatcatgga cagcctgcat     1140

atggccgcca gagagcagca ggtctactgc gaggaaatgc gggaagagag acaggaccgg     1200

ctgaagttca tcgacaagca gctggaactg ctggcccagg actacaagct gcggatcaag     1260

cagatcaccg aagaggtgga aagacaggtg tccaccgcta tggccgagga aatcagacgg     1320

ctgagcgtgc tggtcgacga ctaccagatg gactttcacc cctctccagt ggtgctgaaa     1380

gtctacaaaa acgagctgca ccggcacatc gaggaaggcc tgggcagaaa catgagcgac     1440

agatgcagca ccgccatcac caatagcctg cagaccatgc agcaggacat gatcgacggc     1500

ctgaaacctc tgctgcctgt gtccgtcaga tcccagatcg atatgctggt gccccggcag     1560

tgctttagcc tgaactacga cctgaactgc gacaagctgt gcgccgattt ccaagaggac     1620

atcgagtttc acttcagcct cggctggaca atgctggtca acagatttct gggccccaag     1680

aacagcagac gggccctgat gggctacaac gatcaggtgc agaggcccat tcctctgaca     1740

cccgccaatc ctagcatgcc tccactgcct cagggcagcc tgacacaaga ggaattcatg     1800

gtgtctatgg tcaccggcct ggccagcctg accagcagaa catctatggg catcctggtc     1860

gtcggcggcg ttgtgtggaa agctgttggc tggcggctga tcgccctgag ctttggcctg     1920

tatggcctgc tgtacgtgta cgagagactg acctggacca ccaaggccaa agagcgggcc     1980

ttcaagcggc agtttgtgga acacgcctcc gagaaactgc agctggtgat cagctacacc     2040

ggcagcaatt gcagccacca ggtgcagcaa gagctgtccg gaacattcgc ccacctgtgt     2100

cagcaggtcg acgtgaccag agagaacctg gaacaagaga tcgccgccat gaataagaaa     2160

atcgaggtgc tcgactccct gcagagcaag gccaagctgc tgagaaacaa ggccggctgg     2220

ctggacagcg agctgaatat gttcacccac cagtacctgc agcctagccg ctaa           2274


<210>  12
<211>  2271
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rMfn2 engineered nucleic acid sequence encoding mitofusin 2 
       protein

<400>  12
atgtctctgc tgttcagccg gtgcaacagc atcgtgaccg tgaagaaaga caagaggcac       60

atggccgaag tgaacgcctc tccactgaag cacttcgtga ccgccaagaa gaagatcaac      120

ggcatcttcg agcagctggg cgcctacatc caagagtctg ccggcttcct ggaagatacc      180

cacagaaaca ccgagctgga ccccgtgacc acagaggaac aggtgctgga cgtgaagggc      240

tacctgtcta aagtgcgggg catcagcgag gtgctggcta gaaggcatat gaaggtggcc      300

tttttcggca ggaccagcaa cggcaagagc accgtgatca acgccatgct gtgggacaaa      360

gtgctgcctt ctggcatcgg ccacaccacc aactgctttc tgagagtcgg cggcacagac      420

ggccacgagg cttttttgct gaccgagggc tccgaagaga agaaatccgt gaaaaccgtg      480

aaccagctgg cccacgctct gcaccaggat gaacaactgc acgccggaag cctggtgtcc      540

gtgatgtggc ctaacagcaa gtgccctctg ctgaaggacg acctggtgct gatggactct      600

cctggaatcg acgtgaccac tgagctggac agctggatcg acaagttctg cctggacgcc      660

gacgtgttcg tgctggtggc taactctgag agcaccctga tgcagaccga gaagcagttc      720

ttccacaagg tgtccgagag gctgagcagg cccaatatct ttatcctgaa caacagatgg      780

gacgccagcg ccagcgagcc cgagtatatg gaagaagtgc ggaggcagca tatggaaagg      840

tgtaccagct tcctggtgga cgagctggga gtcgtggata gagcacaggc cggcgacaga      900

atcttcttcg tgtctgccaa agaggtgctg agcgccaggg tgcagaaagc ccagggaatg      960

cctgaaggcg gcggagcttt ggccgaggga tttcaagtgc ggatgttcga gttccagaac     1020

ttcgagcgga gattcgagga atgcatcagc cagagcgccg tcaagacaaa gttcgagcag     1080

cacacagtgc gggccaagca gatcgctgag gctgtgcggc tgatcatgga cagcctgcat     1140

atcgccgctc aagagcagag ggtgtactgc ctggaaatgc gggaagagag gcaggacagg     1200

ctgagattca tcgacaagca gctggaactg ctggcccagg actacaagct gaggatcaag     1260

cagatgaccg aagaggtgga aagacaggtg tccaccgcca tggccgagga aatccgtaga     1320

ctgtctgtgc tggtcgacga gtaccagatg gactttcacc cctctccagt ggtgctgaag     1380

gtctacaaaa acgagctgca caggcacatc gaggaaggcc tgggcagaaa catgagcgac     1440

aggtgctcta ccgctatcgc cagcagcctg cagacaatgc agcaggacat gatcgacggc     1500

ctgaagcctc tgctgcctgt gtctgtgcgg aaccagatcg atatgctggt gcccaggcag     1560

tgcttctccc tgtcctacga cctgaactgc gacaagctgt gtgccgactt ccaagaggac     1620

atcgagtttc acttcagcct cggctggaca atgctggtca acagattcct gggacctaag     1680

aactccagac gggccctgct gggatacaac gatcaggtgc aaaggcccct gcctctgaca     1740

ccagctaacc cttctatgcc tcctctgcct caaggctctc tgacccaaga ggaactgatg     1800

gtgtccatgg tcacaggcct ggcttccctg accagcagaa cctctatggg catcctggtc     1860

gtcggcggag ttgtgtggaa agctgttggc tggcgcctga tcgccctgag ctttggactg     1920

tacggactgc tgtacgtgta cgagagactg acctggacca ccagggccaa agagagggcc     1980

ttcaagaggc agttcgtgga atacgcctcc gagaaactgc agctgattat ctcctacacc     2040

ggcagcaact gcagccacca ggtgcagcaa gagctgtctg gaacattcgc ccacctgtgc     2100

cagcaggtcg acatcaccag agacaacctg gaacaagaga tcgccgctat gaataagaag     2160

gtggaagccc tggactccct gcagagcaag gctaagctgc tgagaaacaa ggccggctgg     2220

ctggactccg agctgaatat gtttatccac cagtacctgc agcctagccg c              2271


<210>  13
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5'flank

<400>  13
ctggaggctt gctgaaggct gta                                               23


<210>  14
<211>  44
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3'flank

<400>  14
caggacacaa ggcctgttac tagcactcac atggaacaaa tggc                        44


<210>  15
<211>  64
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hMfn2 miR1693

<400>  15
tgctgttctt ataaaccttg aggactgttt tggccactga ctgacagtcc tcagtttata       60

agaa                                                                    64


<210>  16
<211>  64
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rMfn2 miR1518

<400>  16
tgctgttctt ataaaccttg aggacagttt tggccactga ctgactgtcc tcagtttata       60

agaa                                                                    64


<210>  17
<211>  90
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  linker

<400>  17
tgtacaagta aagcgcccgc aggcttgcac ccgtaccttt gggagcgcgc gccctcgtcg       60

tgtcgtgacg tcacccgttc tgttggatcc                                        90


<210>  18
<211>  2274
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hMfn2 endogenous nucleic acid sequence


<220>
<221>  CDS
<222>  (1)..(2274)

<400>  18
atg tcc ctg ctc ttc tct cga tgc aac tct atc gtc aca gtc aag aaa         48
Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys           
1               5                   10                  15                

aat aag aga cac atg gct gag gtg aat gca tcc cca ctt aag cac ttt         96
Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe           
            20                  25                  30                    

gtc act gcc aag aag aag atc aat ggc att ttt gag cag ctg ggg gcc        144
Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala           
        35                  40                  45                        

tac atc cag gag agc gcc acc ttc ctt gaa gac acg tac agg aat gca        192
Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala           
    50                  55                  60                            

gaa ctg gac ccc gtt acc aca gaa gaa cag gtt ctg gac gtc aaa ggt        240
Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly           
65                  70                  75                  80            

tac cta tcc aaa gtg aga ggc atc agt gag gtg ctg gct cgg agg cac        288
Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His           
                85                  90                  95                

atg aaa gtg gct ttt ttt ggc cgg acg agc aat ggg aag agc acc gtg        336
Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val           
            100                 105                 110                   

atc aat gcc atg ctc tgg gac aaa gtt ctg ccc tct ggg att ggc cac        384
Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His           
        115                 120                 125                       

acc acc aat tgc ttc ctg cgg gta gag ggc aca gat ggc cat gag gcc        432
Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala           
    130                 135                 140                           

ttt ctc ctt acc gag ggc tca gag gaa aag agg agt gcc aag act gtg        480
Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val           
145                 150                 155                 160           

aac cag ctg gcc cat gcc ctc cac cag gac aag cag ctc cat gcc ggc        528
Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly           
                165                 170                 175               

agc cta gtg agt gtg atg tgg ccc aac tct aag tgc cca ctt ctg aag        576
Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys           
            180                 185                 190                   

gat gac ctc gtt ttg atg gac agc cct ggt att gat gtc acc aca gag        624
Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu           
        195                 200                 205                       

ctg gac agc tgg att gac aag ttt tgt ctg gat gct gat gtg ttt gtg        672
Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val           
    210                 215                 220                           

ctg gtg gcc aac tca gag tcc acc ctg atg cag acg gaa aag cac ttc        720
Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe           
225                 230                 235                 240           

ttc cac aag gtg agt gag cgt ctc tcc cgg cca aac atc ttc atc ctg        768
Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu           
                245                 250                 255               

aac aac cgc tgg gat gca tct gcc tca gag ccc gag tac atg gag gag        816
Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu           
            260                 265                 270                   

gtg cgg cgg cag cac atg gag cgt tgt acc agc ttc ctg gtg gat gag        864
Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu           
        275                 280                 285                       

ctg ggc gtg gtg gat cga tcc cag gcc ggg gac cgc atc ttc ttt gtg        912
Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val           
    290                 295                 300                           

tct gct aag gag gtg ctc aac gcc agg att cag aaa gcc cag ggc atg        960
Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met           
305                 310                 315                 320           

cct gaa gga ggg ggc gct ctc gca gaa ggc ttt caa gtg agg atg ttt       1008
Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe           
                325                 330                 335               

gag ttt cag aat ttt gag agg aga ttt gag gag tgc atc tcc cag tct       1056
Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser           
            340                 345                 350                   

gca gtg aag acc aag ttt gag cag cac acg gtc cgg gcc aag cag att       1104
Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile           
        355                 360                 365                       

gca gag gcg gtt cga ctc atc atg gac tcc ctg cac atg gcg gct cgg       1152
Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg           
    370                 375                 380                           

gag cag cag gtt tac tgc gag gaa atg cgt gaa gag cgg caa gac cga       1200
Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg           
385                 390                 395                 400           

ctg aaa ttt att gac aaa cag ctg gag ctc ttg gct caa gac tat aag       1248
Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys           
                405                 410                 415               

ctg cga att aag cag att acg gag gaa gtg gag agg cag gtg tcg act       1296
Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr           
            420                 425                 430                   

gca atg gcc gag gag atc agg cgc ctc tct gta ctg gtg gac gat tac       1344
Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr           
        435                 440                 445                       

cag atg gac ttc cac cct tct cca gta gtc ctc aag gtt tat aag aat       1392
Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn           
    450                 455                 460                           

gag ctg cac cgc cac ata gag gaa gga ctg ggt cga aac atg tct gac       1440
Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp           
465                 470                 475                 480           

cgc tgc tcc acg gcc atc acc aac tcc ctg cag acc atg cag cag gac       1488
Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp           
                485                 490                 495               

atg ata gat ggc ttg aaa ccc ctc ctt cct gtg tct gtg cgg agt cag       1536
Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln           
            500                 505                 510                   

ata gac atg ctg gtc cca cgc cag tgc ttc tcc ctc aac tat gac cta       1584
Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu           
        515                 520                 525                       

aac tgt gac aag ctg tgt gct gac ttc cag gaa gac att gag ttc cat       1632
Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His           
    530                 535                 540                           

ttc tct ctc gga tgg acc atg ctg gtg aat agg ttc ctg ggc ccc aag       1680
Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys           
545                 550                 555                 560           

aac agc cgt cgg gcc ttg atg ggc tac aat gac cag gtc cag cgt ccc       1728
Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro           
                565                 570                 575               

atc cct ctg acg cca gcc aac ccc agc atg ccc cca ctg cca cag ggc       1776
Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly           
            580                 585                 590                   

tcg ctc acc cag gag gag ttc atg gtt tcc atg gtt acc ggc ctg gcc       1824
Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala           
        595                 600                 605                       

tcc ttg aca tcc agg acc tcc atg ggc att ctt gtt gtt gga gga gtg       1872
Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val           
    610                 615                 620                           

gtg tgg aag gca gtg ggc tgg cgg ctc att gcc ctc tcc ttt ggg ctc       1920
Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu           
625                 630                 635                 640           

tat ggc ctc ctc tac gtc tat gag cgt ctg acc tgg acc acc aag gcc       1968
Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala           
                645                 650                 655               

aag gag agg gcc ttc aag cgc cag ttt gtg gag cat gcc agc gag aag       2016
Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys           
            660                 665                 670                   

ctg cag ctt gtc atc agc tac act ggc tcc aac tgc agc cac caa gtc       2064
Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val           
        675                 680                 685                       

cag cag gaa ctg tct ggg acc ttt gct cat ctg tgt cag caa gtt gac       2112
Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp           
    690                 695                 700                           

gtc acc cgg gag aac ctg gag cag gaa att gcc gcc atg aac aag aaa       2160
Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys           
705                 710                 715                 720           

att gag gtt ctt gac tca ctt cag agc aaa gca aag ctg ctc agg aat       2208
Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn           
                725                 730                 735               

aaa gcc ggt tgg ttg gac agt gag ctc aac atg ttc aca cac cag tac       2256
Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr           
            740                 745                 750                   

ctg cag ccc agc aga tag                                               2274
Leu Gln Pro Ser Arg                                                       
        755                                                               


<210>  19
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  19

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  20
<211>  2274
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rMfn2 endogenous nucleic acid sequence


<220>
<221>  CDS
<222>  (1)..(2274)

<400>  20
atg tcc ctg ctc ttt tct cga tgc aac tcc atc gtc acc gtc aag aag         48
Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys           
1               5                   10                  15                

gat aag cga cac atg gct gag gtg aat gct tcc cct ctc aag cac ttt         96
Asp Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe           
            20                  25                  30                    

gtc act gcc aag aaa aag atc aat ggc atc ttt gag cag ctg ggg gcc        144
Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala           
        35                  40                  45                        

tac atc caa gag agt gcc ggc ttc ctt gaa gac acc cac agg aat aca        192
Tyr Ile Gln Glu Ser Ala Gly Phe Leu Glu Asp Thr His Arg Asn Thr           
    50                  55                  60                            

gaa ctg gac cca gtt act aca gaa gag cag gtc ctg gat gtc aaa ggg        240
Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly           
65                  70                  75                  80            

tac ctg tcc aag gtc agg gga atc agc gag gtg ctg gcc agg cgg cac        288
Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His           
                85                  90                  95                

atg aag gtg gct ttt ttt ggc cgg acg agc aat ggg aag agc acc gtg        336
Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val           
            100                 105                 110                   

atc aat gcc atg ctt tgg gac aaa gtt ctg cca tct ggg att ggc cac        384
Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His           
        115                 120                 125                       

acc acc aat tgc ttc ctg cgg gtt ggg ggc acg gat ggc cac gag gcc        432
Thr Thr Asn Cys Phe Leu Arg Val Gly Gly Thr Asp Gly His Glu Ala           
    130                 135                 140                           

ttc ctc ctc acg gag ggc tca gaa gag aag aag agt gtc aag acc gtg        480
Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Lys Ser Val Lys Thr Val           
145                 150                 155                 160           

aac cag cta gcc cat gcc ctc cat cag gat gag cag ctg cat gca ggc        528
Asn Gln Leu Ala His Ala Leu His Gln Asp Glu Gln Leu His Ala Gly           
                165                 170                 175               

agc ctg gtg agt gtg atg tgg ccc aac tcc aag tgt cca ctt ctg aag        576
Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys           
            180                 185                 190                   

gat gac ctc gtg ctg atg gac agc cct ggg atc gat gtc acc acg gag        624
Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu           
        195                 200                 205                       

ctg gac agc tgg att gat aag ttt tgc ctg gat gct gat gtg ttt gta        672
Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val           
    210                 215                 220                           

ctg gtg gcc aac tca gag tcc acg ctg atg cag acg gag aag cag ttc        720
Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys Gln Phe           
225                 230                 235                 240           

ttc cac aaa gtg agt gag cgt ctc tcc cgg ccc aac atc ttc atc ctg        768
Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu           
                245                 250                 255               

aac aac cgc tgg gat gcg tct gcc tcg gag cct gag tac atg gag gag        816
Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu           
            260                 265                 270                   

gtg cgg cgg cag cac atg gaa cgc tgc acc agc ttt ctg gtg gat gag        864
Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu           
        275                 280                 285                       

cta ggc gtg gtg gat cga gct cag gcc ggg gac cgg atc ttc ttt gtg        912
Leu Gly Val Val Asp Arg Ala Gln Ala Gly Asp Arg Ile Phe Phe Val           
    290                 295                 300                           

tct gcc aag gag gtg ctc agt gcc agg gtc cag aaa gcc cag ggc atg        960
Ser Ala Lys Glu Val Leu Ser Ala Arg Val Gln Lys Ala Gln Gly Met           
305                 310                 315                 320           

cca gaa gga ggt ggc gct ctt gca gaa ggt ttt caa gtg agg atg ttt       1008
Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe           
                325                 330                 335               

gag ttt cag aat ttc gag agg cga ttt gag gag tgc att tcc cag tct       1056
Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser           
            340                 345                 350                   

gca gta aag acc aaa ttt gag cag cac aca gtc cgg gcc aag cag att       1104
Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile           
        355                 360                 365                       

gca gag gcc gtc cgt ctc atc atg gat tcc ctg cac att gcg gct cag       1152
Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Ile Ala Ala Gln           
    370                 375                 380                           

gag cag cgg gtt tat tgt ctt gaa atg cgg gaa gag cgg caa gac cgg       1200
Glu Gln Arg Val Tyr Cys Leu Glu Met Arg Glu Glu Arg Gln Asp Arg           
385                 390                 395                 400           

ctg aga ttc att gac aag cag ctg gag ctc ctg gct caa gac tat aag       1248
Leu Arg Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys           
                405                 410                 415               

cta cgg att aag cag atg aca gag gaa gtg gaa agg cag gtg tcc aca       1296
Leu Arg Ile Lys Gln Met Thr Glu Glu Val Glu Arg Gln Val Ser Thr           
            420                 425                 430                   

gcc atg gct gaa gag atc agg cgc ctc tct gtg ctg gtt gac gag tac       1344
Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Glu Tyr           
        435                 440                 445                       

cag atg gac ttt cac cca tcc cca gtt gtc ctc aag gtt tat aag aat       1392
Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn           
    450                 455                 460                           

gaa ctg cac cgc cat ata gag gaa ggc ctg gga cga aac atg tct gac       1440
Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp           
465                 470                 475                 480           

cgc tgc tcc aca gcc att gcc agt tca ctg cag act atg cag caa gac       1488
Arg Cys Ser Thr Ala Ile Ala Ser Ser Leu Gln Thr Met Gln Gln Asp           
                485                 490                 495               

atg ata gac ggc ttg aag ccc ctt ctt cct gtg tct gtg cgg aat cag       1536
Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Asn Gln           
            500                 505                 510                   

ata gac atg ctg gtc cct cga cag tgt ttc tcc ctc agc tat gac ctg       1584
Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Ser Tyr Asp Leu           
        515                 520                 525                       

aac tgt gac aag ctg tgc gct gac ttt cag gag gac atc gaa ttc cat       1632
Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His           
    530                 535                 540                           

ttc tcc ctt gga tgg act atg cta gtg aat agg ttc ctg ggc cct aag       1680
Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys           
545                 550                 555                 560           

aat agc cgg cgg gcc ttg ctg ggc tac aat gat cag gtt cag cgt cct       1728
Asn Ser Arg Arg Ala Leu Leu Gly Tyr Asn Asp Gln Val Gln Arg Pro           
                565                 570                 575               

ctc cct ctg aca cct gcc aac ccc agc atg cca ccc ttg cca cag ggc       1776
Leu Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly           
            580                 585                 590                   

tcc ctc acc cag gag gag ctc atg gtc tcc atg gtt act ggc ctg gcc       1824
Ser Leu Thr Gln Glu Glu Leu Met Val Ser Met Val Thr Gly Leu Ala           
        595                 600                 605                       

tct ctg act tcc agg acc tct atg ggc att ctc gtg gtc gga gga gtg       1872
Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val           
    610                 615                 620                           

gtg tgg aag gca gtg ggc tgg aga ctc atc gcc ctc tcc ttt gga ctg       1920
Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu           
625                 630                 635                 640           

tat ggc ctc ctg tac gtg tat gag cgg ctg acc tgg acc acc aga gcc       1968
Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Arg Ala           
                645                 650                 655               

aag gag agg gcc ttc aag cgc cag ttt gtg gag tat gcc agt gag aag       2016
Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu Tyr Ala Ser Glu Lys           
            660                 665                 670                   

ctg cag ctc att atc agt tat acc ggc tct aac tgc agc cac caa gtt       2064
Leu Gln Leu Ile Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val           
        675                 680                 685                       

cag caa gaa ttg tct ggg aca ttt gct cat ctg tgc cag caa gtt gac       2112
Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp           
    690                 695                 700                           

atc acc cgg gat aat ctg gag cag gaa att gct gcc atg aac aag aaa       2160
Ile Thr Arg Asp Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys           
705                 710                 715                 720           

gtt gag gct ctg gat tca ctt cag agc aaa gcc aaa ttg ctc agg aat       2208
Val Glu Ala Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn           
                725                 730                 735               

aaa gct ggc tgg ttg gac agc gaa ctc aac atg ttc ata cac cag tac       2256
Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Ile His Gln Tyr           
            740                 745                 750                   

ctg cag ccc agc aga tag                                               2274
Leu Gln Pro Ser Arg                                                       
        755                                                               


<210>  21
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  21

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asp Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Gly Phe Leu Glu Asp Thr His Arg Asn Thr 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Gly Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Lys Ser Val Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Glu Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys Gln Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ala Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Ser Ala Arg Val Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Ile Ala Ala Gln 
    370                 375                 380                 


Glu Gln Arg Val Tyr Cys Leu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Arg Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Met Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Glu Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Ala Ser Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Asn Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Ser Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Leu Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Leu Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Leu Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Arg Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu Tyr Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Ile Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Ile Thr Arg Asp Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Val Glu Ala Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Ile His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  22
<211>  215
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  bGH polyA

<400>  22
gcctcgactg tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc       60

ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg      120

cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg      180

gaggattggg aagacaatag caggcatgct gggga                                 215


<210>  23
<211>  232
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SV40 polyA

<400>  23
cgagcagaca tgataagata cattgatgag tttggacaaa ccacaactag aatgcagtga       60

aaaaaatgct ttatttgtga aatttgtgat gctattgctt tatttgtaac cattataagc      120

tgcaataaac aagttaacaa caacaattgc attcatttta tgtttcaggt tcagggggag      180

atgtgggagg ttttttaaag caagtaaaac ctctacaaat gtggtaaaat cg              232


<210>  24
<211>  2315
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hMfn2 engineered nucleic acid sequnece V1


<220>
<221>  CDS
<222>  (1)..(2274)

<400>  24
gct agc acc ggt gcc acc atg agc ctg ctg ttc agc cgg tgc aac agc         48
Ala Ser Thr Gly Ala Thr Met Ser Leu Leu Phe Ser Arg Cys Asn Ser           
1               5                   10                  15                

atc gtg acc gtg aag aaa aac aag cgg cac atg gcc gaa gtg aac gcc         96
Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn Ala           
            20                  25                  30                    

tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac ggc atc        144
Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile           
        35                  40                  45                        

ttc gag cag ctg ggc gcc tac atc caa gag agc gcc acc ttc ctg gaa        192
Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu           
    50                  55                  60                            

gat acc tac aga aac gcc gag ctg gac ccc gtg acc aca gag gaa cag        240
Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu Gln           
65                  70                  75                  80            

gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg ggc atc tct gaa        288
Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu           
                85                  90                  95                

gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc ggc cgg acc agc        336
Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser           
            100                 105                 110                   

aac ggc aag agc acc gtg atc aat gcc atg ctg tgg gac aaa gtg ctg        384
Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu           
        115                 120                 125                       

ccc tct gga atc ggc cac acc acc aac tgc ttt ctg aga gtg gaa ggc        432
Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu Gly           
    130                 135                 140                           

acc gac ggc cac gag gca ttt ctg ctg aca gag ggc tcc gag gaa aag        480
Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys           
145                 150                 155                 160           

cgg agc gcc aag aca gtg aac cag ctg gcc cat gct ctg cac cag gat        528
Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp           
                165                 170                 175               

aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg tgg ccc aat agc        576
Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser           
            180                 185                 190                   

aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gat agc ccc ggg        624
Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly           
        195                 200                 205                       

atc gat gtg acc acc gaa ctg gac agc tgg atc gac aag ttc tgc ctg        672
Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu           
    210                 215                 220                           

gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag agc acc ctg atg        720
Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met           
225                 230                 235                 240           

cag acc gag aag cac ttt ttc cac aag gtg tcc gag cgg ctg agc aga        768
Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg           
                245                 250                 255               

ccc aac aat ttt atc ctg aac aac aga tgg gac gcc agc gcc agc gag        816
Pro Asn Asn Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu           
            260                 265                 270                   

ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg gaa cgg tgc aca        864
Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr           
        275                 280                 285                       

tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga tct cag gcc ggc        912
Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala Gly           
    290                 295                 300                           

gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg aac gcc cgg att        960
Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg Ile           
305                 310                 315                 320           

cag aaa gcc cag gga atg cct gaa ggc gga ggt gca ctg gcc gag gga       1008
Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly           
                325                 330                 335               

ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc gag       1056
Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu           
            340                 345                 350                   

gaa tgc atc agc cag agc gcc gtc aag acc aag ttt gag cag cat acc       1104
Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr           
        355                 360                 365                       

gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg atc atg gac agc       1152
Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser           
    370                 375                 380                           

ctg cat atg gcc gcc aga gag cag cag gtc tac tgc gag gaa atg cgg       1200
Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met Arg           
385                 390                 395                 400           

gaa gag aga cag gac cgg ctg aag ttc atc gac aag cag ctg gaa ctg       1248
Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu           
                405                 410                 415               

ctg gcc cag gac tac aag ctg cgg atc aag cag atc acc gaa gag gtg       1296
Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu Val           
            420                 425                 430                   

gaa aga cag gtg tcc acc gct atg gcc gag gaa atc aga cgg ctg agc       1344
Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser           
        435                 440                 445                       

gtg ctg gtc gac gac tac cag atg gac ttt cac ccc tct cca gtg gtg       1392
Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val Val           
    450                 455                 460                           

ctg aag gtc tac aag aac gag ctg cac cgg cac atc gag gaa ggc ctg       1440
Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu           
465                 470                 475                 480           

ggc aga aac atg agc gac aga tgc agc acc gcc atc acc aat agc ctg       1488
Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu           
                485                 490                 495               

cag acc atg cag cag gac atg atc gac ggc ctg aaa cct ctg ctg cct       1536
Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro           
            500                 505                 510                   

gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc cgg cag tgc ttt       1584
Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe           
        515                 520                 525                       

agc ctg aac tac gac ctg aac tgc gac aag ctg tgc gcc gat ttc caa       1632
Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln           
    530                 535                 540                           

gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc aac       1680
Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn           
545                 550                 555                 560           

aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg atg ggc tac aac       1728
Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn           
                565                 570                 575               

gat cag gtg cag agg ccc att cct ctg aca ccc gcc aat cct agc atg       1776
Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser Met           
            580                 585                 590                   

cct cca ctg cct cag ggc agc ctg aca caa gag gaa ttc atg gtg tct       1824
Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val Ser           
        595                 600                 605                       

atg gtc acc ggc ctg gcc agc ctg acc agc aga aca tct atg ggc atc       1872
Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile           
    610                 615                 620                           

ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc tgg cgg ctg atc       1920
Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile           
625                 630                 635                 640           

gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg tac gag aga ctg       1968
Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu           
                645                 650                 655               

acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag cgg cag ttt gtg       2016
Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val           
            660                 665                 670                   

gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc tac acc ggc agc       2064
Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser           
        675                 680                 685                       

aat tgc agc cac cag gtg cag caa gag ctg tcc gga aca ttc gcc cac       2112
Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His           
    690                 695                 700                           

ctg tgt cag cag gtc gac gtg acc aga gag aac ctg gaa caa gag atc       2160
Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu Ile           
705                 710                 715                 720           

gcc gcc atg aac aag aaa atc gag gtg ctc gac tcc ctg cag agc aag       2208
Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser Lys           
                725                 730                 735               

gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac agc gag ctg aat       2256
Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn           
            740                 745                 750                   

atg ttc acc cac cag tac ctgcagccta gccgctaata atgtacagcg              2304
Met Phe Thr His Gln Tyr                                                   
        755                                                               

gccgcaagct t                                                          2315


<210>  25
<211>  758
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  25

Ala Ser Thr Gly Ala Thr Met Ser Leu Leu Phe Ser Arg Cys Asn Ser 
1               5                   10                  15      


Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn Ala 
            20                  25                  30          


Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile 
        35                  40                  45              


Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu 
    50                  55                  60                  


Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu Gln 
65                  70                  75                  80  


Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu 
                85                  90                  95      


Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser 
            100                 105                 110         


Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu 
        115                 120                 125             


Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu Gly 
    130                 135                 140                 


Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys 
145                 150                 155                 160 


Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp 
                165                 170                 175     


Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser 
            180                 185                 190         


Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly 
        195                 200                 205             


Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu 
    210                 215                 220                 


Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met 
225                 230                 235                 240 


Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg 
                245                 250                 255     


Pro Asn Asn Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu 
            260                 265                 270         


Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr 
        275                 280                 285             


Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala Gly 
    290                 295                 300                 


Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg Ile 
305                 310                 315                 320 


Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly 
                325                 330                 335     


Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu 
            340                 345                 350         


Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr 
        355                 360                 365             


Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser 
    370                 375                 380                 


Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met Arg 
385                 390                 395                 400 


Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu 
                405                 410                 415     


Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu Val 
            420                 425                 430         


Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser 
        435                 440                 445             


Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val Val 
    450                 455                 460                 


Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu 
465                 470                 475                 480 


Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu 
                485                 490                 495     


Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro 
            500                 505                 510         


Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe 
        515                 520                 525             


Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln 
    530                 535                 540                 


Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn 
545                 550                 555                 560 


Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn 
                565                 570                 575     


Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser Met 
            580                 585                 590         


Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val Ser 
        595                 600                 605             


Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile 
    610                 615                 620                 


Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile 
625                 630                 635                 640 


Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu 
                645                 650                 655     


Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val 
            660                 665                 670         


Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser 
        675                 680                 685             


Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His 
    690                 695                 700                 


Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu Ile 
705                 710                 715                 720 


Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser Lys 
                725                 730                 735     


Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn 
            740                 745                 750         


Met Phe Thr His Gln Tyr 
        755             


<210>  26
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  26
aaaccttgag gactactgga g                                                 21


<210>  27
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  27
ttgacgtcca gaacctgttc t                                                 21


<210>  28
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  28
agaagtgggc acttagagtt g                                                 21


<210>  29
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  29
ttcagaagtg ggcacttaga g                                                 21


<210>  30
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  30
ttgtcaatcc agctgtccag c                                                 21


<210>  31
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  31
caaacttggt cttcactgca g                                                 21


<210>  32
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  32
aaaccttgag gactactgga g                                                 21


<210>  33
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  33
taaccatgga aaccatgaac t                                                 21


<210>  34
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  34
acaacaagaa tgcccatgga g                                                 21


<210>  35
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  35
aaaggtccca gacagttcct g                                                 21


<210>  36
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  36
tgttcatggc ggcaatttcc t                                                 21


<210>  37
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  37
tgaggttggc tattgattga c                                                 21


<210>  38
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  38
ttctcacaca gtcaacacct t                                                 21


<210>  39
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  39
tttcctcgca gtaaacctgc t                                                 21


<210>  40
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  40
agaaatggaa ctcaatgtct t                                                 21


<210>  41
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  41
tgaacaggac atcacctgtg a                                                 21


<210>  42
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  42
aatacaagca ggtatgtgaa c                                                 21


<210>  43
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  43
taaacctgct gctcccgagc c                                                 21


<210>  44
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  44
tagaggaggc catagagccc a                                                 21


<210>  45
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  45
tctacccgca ggaagcaatt g                                                 21


<210>  46
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  antisense sequence

<400>  46
ctccttagca gacacaaaga a                                                 21


<210>  47
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  47
agaacaggtt ctggacgtca a                                                 21


<210>  48
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  48
caactctaag tgcccacttc t                                                 21


<210>  49
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  49
ctctaagtgc ccacttctga a                                                 21


<210>  50
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  50
gctggacagc tggattgaca a                                                 21


<210>  51
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  51
ctgcagtgaa gaccaagttt g                                                 21


<210>  52
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  52
ctccagtagt cctcaaggtt t                                                 21


<210>  53
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  53
agttcatggt ttccatggtt a                                                 21


<210>  54
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  54
ctccatgggc attcttgttg t                                                 21


<210>  55
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  55
caggaactgt ctgggacctt t                                                 21


<210>  56
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  56
aggaaattgc cgccatgaac a                                                 21


<210>  57
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  57
agtcctcaag gtttataaga a                                                 21


<210>  58
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  58
gtcaatcaat agccaacctc a                                                 21


<210>  59
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  59
aaggtgttga ctgtgtgaga a                                                 21


<210>  60
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  60
agcaggttta ctgcgaggaa a                                                 21


<210>  61
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  61
aagacattga gttccatttc t                                                 21


<210>  62
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  62
tcacaggtga tgtcctgttc a                                                 21


<210>  63
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  63
gttcacatac ctgcttgtat t                                                 21


<210>  64
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  64
ggctcgggag cagcaggttt a                                                 21


<210>  65
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  65
tgggctctat ggcctcctct a                                                 21


<210>  66
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  66
caattgcttc ctgcgggtag a                                                 21


<210>  67
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Target hMfn2 Sequence

<400>  67
ttctttgtgt ctgctaagga g                                                 21


<210>  68
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  miR1693(21-mer)

<400>  68
ttcttataaa ccttgaggac t                                                 21


<210>  69
<211>  4771
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector genome CAG.CI.hMfn2.GA.link.miR538.WPRE.SV40


<220>
<221>  repeat_region
<222>  (1)..(188)
<223>  5'ITR

<220>
<221>  misc_feature
<222>  (192)..(1032)
<223>  CAG(CBA)

<220>
<221>  enhancer
<222>  (194)..(436)
<223>  CMV enhancer

<220>
<221>  promoter
<222>  (439)..(720)
<223>  CB promoter

<220>
<221>  Intron
<222>  (720)..(1127)
<223>  Hybrid Intron in CAG

<220>
<221>  Intron
<222>  (720)..(950)
<223>  b-actin intron

<220>
<221>  misc_feature
<222>  (1158)..(1163)
<223>  Kozak

<220>
<221>  CDS
<222>  (1164)..(3437)
<223>  human Mfn2 engineered

<220>
<221>  misc_feature
<222>  (1379)..(1399)
<223>  miR538 mut

<220>
<221>  misc_feature
<222>  (2534)..(2554)
<223>  miR1518 mutated

<220>
<221>  misc_feature
<222>  (3438)..(3519)
<223>  linker p4271

<220>
<221>  misc_feature
<222>  (3520)..(3547)
<223>  miR538 AS

<220>
<221>  misc_feature
<222>  (3569)..(3587)
<223>  loop

<220>
<221>  misc_feature
<222>  (3588)..(3606)
<223>  miR538 sense

<220>
<221>  misc_feature
<222>  (3607)..(3651)
<223>  3' flank

<220>
<221>  misc_feature
<222>  (3678)..(4266)
<223>  WRPE

<220>
<221>  misc_feature
<222>  (4355)..(4474)
<223>  SV40 PA temrinator

<220>
<221>  repeat_region
<222>  (4584)..(4771)
<223>  3'ITR

<400>  69
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacgt agccatgctc      180

taggaagagt accattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga      240

ctttccattg acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc      300

aagtgtatca tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct      360

ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat      420

tagtcatcgc tattaccatg gtcgaggtga gccccacgtt ctgcttcact ctccccatct      480

cccccccctc cccaccccca attttgtatt tatttatttt ttaattattt tgtgcagcga      540

tgggggcggg gggggggggg gggcgcgcgc caggcggggc ggggcggggc gaggggcggg      600

gcggggcgag gcggagaggt gcggcggcag ccaatcagag cggcgcgctc cgaaagtttc      660

cttttatggc gaggcggcgg cggcggcggc cctataaaaa gcgaagcgcg cggcgggcgg      720

gagtcgctgc gcgctgcctt cgccccgtgc cccgctccgc cgccgcctcg cgccgcccgc      780

cccggctctg actgaccgcg ttactcccac aggtgagcgg gcgggacggc ccttctcctc      840

cgggctgtaa ttagcgcttg gtttaatgac ggcttgtttc ttttctgtgg ctgcgtgaaa      900

gccttgaggg gctccgggag ggccctttgt gcggggggag cggctcgggg ctgtccgcgg      960

ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg gcgtgtgacc     1020

ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct acagctcctg     1080

ggcaacgtgc tggttattgt gctgtctcat cattttggca aagaattgga tcccgtacga     1140

cgcgtgctag caccggtgcc acc atg agc ctg ctg ttc agc cgg tgc aac agc     1193
                          Met Ser Leu Leu Phe Ser Arg Cys Asn Ser         
                          1               5                   10          

atc gtg acc gtg aag aaa aac aag cgg cac atg gcc gaa gtg aac gcc       1241
Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn Ala           
                15                  20                  25                

tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac ggc atc       1289
Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile           
            30                  35                  40                    

ttc gag cag ctg ggc gcc tac atc caa gag agc gcc acc ttc ctg gaa       1337
Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu           
        45                  50                  55                        

gat acc tac aga aac gcc gag ctg gac ccc gtg acc aca gag gaa cag       1385
Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu Gln           
    60                  65                  70                            

gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg ggc atc tct gaa       1433
Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu           
75                  80                  85                  90            

gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc ggc cgg acc agc       1481
Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser           
                95                  100                 105               

aac ggc aag agc acc gtg atc aat gcc atg ctg tgg gac aaa gtg ctg       1529
Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu           
            110                 115                 120                   

ccc tct gga atc ggc cac acc acc aac tgc ttt ctg aga gtg gaa ggc       1577
Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu Gly           
        125                 130                 135                       

acc gac ggc cac gag gca ttt ctg ctg aca gag ggc tcc gag gaa aag       1625
Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys           
    140                 145                 150                           

cgg agc gcc aag aca gtg aac cag ctg gcc cat gct ctg cac cag gat       1673
Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp           
155                 160                 165                 170           

aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg tgg ccc aat agc       1721
Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser           
                175                 180                 185               

aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gat agc ccc ggg       1769
Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly           
            190                 195                 200                   

atc gat gtg acc acc gaa ctg gac agc tgg atc gac aag ttc tgc ctg       1817
Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu           
        205                 210                 215                       

gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag agc acc ctg atg       1865
Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met           
    220                 225                 230                           

cag acc gag aag cac ttt ttc cac aag gtg tcc gag cgg ctg agc aga       1913
Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg           
235                 240                 245                 250           

ccc aat atc ttt atc ctg aac aac aga tgg gac gcc agc gcc agc gag       1961
Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu           
                255                 260                 265               

ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg gaa cgg tgc aca       2009
Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr           
            270                 275                 280                   

tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga tct cag gcc ggc       2057
Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala Gly           
        285                 290                 295                       

gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg aac gcc cgg att       2105
Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg Ile           
    300                 305                 310                           

cag aaa gcc cag gga atg cct gaa ggc gga ggt gca ctg gcc gag gga       2153
Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly           
315                 320                 325                 330           

ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc gag       2201
Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu           
                335                 340                 345               

gag tgc atc agc cag agc gcc gtc aag acc aag ttc gag cag cat acc       2249
Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr           
            350                 355                 360                   

gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg atc atg gac agc       2297
Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser           
        365                 370                 375                       

ctg cat atg gcc gcc aga gag cag cag gtc tac tgc gag gaa atg cgg       2345
Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met Arg           
    380                 385                 390                           

gaa gag aga cag gac cgg ctg aag ttc atc gac aag cag ctg gaa ctg       2393
Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu           
395                 400                 405                 410           

ctg gcc cag gac tac aag ctg cgg atc aag cag atc acc gaa gag gtg       2441
Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu Val           
                415                 420                 425               

gaa aga cag gtg tcc acc gct atg gcc gag gaa atc aga cgg ctg agc       2489
Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser           
            430                 435                 440                   

gtg ctg gtc gac gac tac cag atg gac ttt cac ccc tct cca gtg gtg       2537
Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val Val           
        445                 450                 455                       

ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc gag gaa ggc ctg       2585
Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu           
    460                 465                 470                           

ggc aga aac atg agc gac aga tgc agc acc gcc atc acc aat agc ctg       2633
Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu           
475                 480                 485                 490           

cag acc atg cag cag gac atg atc gac ggc ctg aaa cct ctg ctg cct       2681
Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro           
                495                 500                 505               

gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc cgg cag tgc ttt       2729
Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe           
            510                 515                 520                   

agc ctg aac tac gac ctg aac tgc gac aag ctg tgc gcc gat ttc caa       2777
Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln           
        525                 530                 535                       

gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc aac       2825
Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn           
    540                 545                 550                           

aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg atg ggc tac aac       2873
Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn           
555                 560                 565                 570           

gat cag gtg cag agg ccc att cct ctg aca ccc gcc aat cct agc atg       2921
Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser Met           
                575                 580                 585               

cct cca ctg cct cag ggc agc ctg aca caa gag gaa ttc atg gtg tct       2969
Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val Ser           
            590                 595                 600                   

atg gtc acc ggc ctg gcc agc ctg acc agc aga aca tct atg ggc atc       3017
Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile           
        605                 610                 615                       

ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc tgg cgg ctg atc       3065
Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile           
    620                 625                 630                           

gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg tac gag aga ctg       3113
Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu           
635                 640                 645                 650           

acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag cgg cag ttt gtg       3161
Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val           
                655                 660                 665               

gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc tac acc ggc agc       3209
Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser           
            670                 675                 680                   

aat tgc agc cac cag gtg cag caa gag ctg tcc gga aca ttc gcc cac       3257
Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His           
        685                 690                 695                       

ctg tgt cag cag gtc gac gtg acc aga gag aac ctg gaa caa gag atc       3305
Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu Ile           
    700                 705                 710                           

gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc ctg cag agc aag       3353
Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser Lys           
715                 720                 725                 730           

gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac agc gag ctg aat       3401
Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn           
                735                 740                 745               

atg ttc acc cac cag tac ctg cag cct agc cgc taa taaagcggcc            3447
Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg                               
            750                 755                                       

gcaagcttgc acccgtacct ttgggagcgc gcgccctcgt cgtgtcgtga cgtcacccgt     3507

tctgttggat ccctggaggc ttgctgaagg ctgtatgctg ttgacgtcca gaacctgttc     3567

tgttttggcc actgactgac agaacaggct ggacgtcaac aggacacaag gcctgttact     3627

agcactcaca tggaacaaat ggcccagatc ttaagcttct cgagatcgat aatcaacctc     3687

tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct ccttttacgc     3747

tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt atggctttca     3807

ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg tggcccgttg     3867

tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact ggttggggca     3927

ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct attgccacgg     3987

cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg ttgggcactg     4047

acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg     4107

ccacctggat tctgcgcggg acgcccttct gctacgtccc ttcggccctc aatccagcgg     4167

accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc     4227

ctcagacgag tcggatctcc ctttgggccg cctccccgcc tgctgatcgc cctgagcctg     4287

gccctggtga ccaacagcca ggtgcaattg ctagagtcga ctctagagcg gccgcttcga     4347

gcagacatga taagatacat tgatgagttt ggacaaacca caactagaat gcagtgaaaa     4407

aaatgcttta tttgtgaaat ttgtgatgct attgctttat ttgtaaccat tataagctgc     4467

aataaacaag ttaacaacaa caattgcatt cattttatgt ttcaggttca gggggagatg     4527

tgggaggttt tttaaagcaa gtaaaacctc tacaaatgtg gtaaaatcga taaggatctt     4587

cctagagcat ggctacgtag ataagtagca tggcgggtta atcattaact acaaggaacc     4647

cctagtgatg gagttggcca ctccctctct gcgcgctcgc tcgctcactg aggccgggcg     4707

accaaaggtc gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg agcgagcgcg     4767

cagc                                                                  4771


<210>  70
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  70

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  71
<211>  4771
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector genome CAG.CI.hMfn2.GA.link.miR1518.WPRE.SV40


<220>
<221>  repeat_region
<222>  (1)..(188)
<223>  ITR

<220>
<221>  misc_feature
<222>  (192)..(1032)
<223>  CAG (CBA)

<220>
<221>  enhancer
<222>  (194)..(436)
<223>  CMV enhancer

<220>
<221>  promoter
<222>  (439)..(720)
<223>  CB Promoter

<220>
<221>  Intron
<222>  (720)..(1127)
<223>  Hybrid intron in CAG

<220>
<221>  Intron
<222>  (720)..(950)
<223>  b-actin intron

<220>
<221>  misc_feature
<222>  (1158)..(1163)
<223>  Kozak

<220>
<221>  CDS
<222>  (1164)..(3437)
<223>  human Mfn2 optimized

<220>
<221>  misc_feature
<222>  (1379)..(1399)
<223>  miR538 mut

<220>
<221>  misc_feature
<222>  (2534)..(2554)
<223>  miR 1518 mutated

<220>
<221>  misc_feature
<222>  (3438)..(3519)
<223>  linker p4271

<220>
<221>  misc_feature
<222>  (3520)..(3547)
<223>  5' flank

<220>
<221>  misc_feature
<222>  (3569)..(3587)
<223>  loop

<220>
<221>  misc_feature
<222>  (3588)..(3606)
<223>  rat miR 1518 sense

<220>
<221>  misc_feature
<222>  (3607)..(3651)
<223>  3' flank

<220>
<221>  misc_feature
<222>  (3678)..(4266)
<223>  WRPE

<220>
<221>  misc_feature
<222>  (4355)..(4474)
<223>  SV40 PA terminator

<220>
<221>  repeat_region
<222>  (4584)..(4771)
<223>  ITR

<220>
<221>  misc_feature
<222>  (35488)..(3568)
<223>  rat miR1518 AS

<400>  71
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacgt agccatgctc      180

taggaagagt accattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga      240

ctttccattg acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc      300

aagtgtatca tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct      360

ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat      420

tagtcatcgc tattaccatg gtcgaggtga gccccacgtt ctgcttcact ctccccatct      480

cccccccctc cccaccccca attttgtatt tatttatttt ttaattattt tgtgcagcga      540

tgggggcggg gggggggggg gggcgcgcgc caggcggggc ggggcggggc gaggggcggg      600

gcggggcgag gcggagaggt gcggcggcag ccaatcagag cggcgcgctc cgaaagtttc      660

cttttatggc gaggcggcgg cggcggcggc cctataaaaa gcgaagcgcg cggcgggcgg      720

gagtcgctgc gcgctgcctt cgccccgtgc cccgctccgc cgccgcctcg cgccgcccgc      780

cccggctctg actgaccgcg ttactcccac aggtgagcgg gcgggacggc ccttctcctc      840

cgggctgtaa ttagcgcttg gtttaatgac ggcttgtttc ttttctgtgg ctgcgtgaaa      900

gccttgaggg gctccgggag ggccctttgt gcggggggag cggctcgggg ctgtccgcgg      960

ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg gcgtgtgacc     1020

ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct acagctcctg     1080

ggcaacgtgc tggttattgt gctgtctcat cattttggca aagaattgga tcccgtacga     1140

cgcgtgctag caccggtgcc acc atg agc ctg ctg ttc agc cgg tgc aac agc     1193
                          Met Ser Leu Leu Phe Ser Arg Cys Asn Ser         
                          1               5                   10          

atc gtg acc gtg aag aaa aac aag cgg cac atg gcc gaa gtg aac gcc       1241
Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn Ala           
                15                  20                  25                

tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac ggc atc       1289
Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile           
            30                  35                  40                    

ttc gag cag ctg ggc gcc tac atc caa gag agc gcc acc ttc ctg gaa       1337
Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu           
        45                  50                  55                        

gat acc tac aga aac gcc gag ctg gac ccc gtg acc aca gag gaa cag       1385
Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu Gln           
    60                  65                  70                            

gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg ggc atc tct gaa       1433
Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu           
75                  80                  85                  90            

gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc ggc cgg acc agc       1481
Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser           
                95                  100                 105               

aac ggc aag agc acc gtg atc aat gcc atg ctg tgg gac aaa gtg ctg       1529
Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu           
            110                 115                 120                   

ccc tct gga atc ggc cac acc acc aac tgc ttt ctg aga gtg gaa ggc       1577
Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu Gly           
        125                 130                 135                       

acc gac ggc cac gag gca ttt ctg ctg aca gag ggc tcc gag gaa aag       1625
Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys           
    140                 145                 150                           

cgg agc gcc aag aca gtg aac cag ctg gcc cat gct ctg cac cag gat       1673
Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp           
155                 160                 165                 170           

aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg tgg ccc aat agc       1721
Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser           
                175                 180                 185               

aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gat agc ccc ggg       1769
Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly           
            190                 195                 200                   

atc gat gtg acc acc gaa ctg gac agc tgg atc gac aag ttc tgc ctg       1817
Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu           
        205                 210                 215                       

gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag agc acc ctg atg       1865
Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met           
    220                 225                 230                           

cag acc gag aag cac ttt ttc cac aag gtg tcc gag cgg ctg agc aga       1913
Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg           
235                 240                 245                 250           

ccc aat atc ttt atc ctg aac aac aga tgg gac gcc agc gcc agc gag       1961
Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu           
                255                 260                 265               

ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg gaa cgg tgc aca       2009
Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr           
            270                 275                 280                   

tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga tct cag gcc ggc       2057
Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala Gly           
        285                 290                 295                       

gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg aac gcc cgg att       2105
Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg Ile           
    300                 305                 310                           

cag aaa gcc cag gga atg cct gaa ggc gga ggt gca ctg gcc gag gga       2153
Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly           
315                 320                 325                 330           

ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc gag       2201
Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu           
                335                 340                 345               

gag tgc atc agc cag agc gcc gtc aag acc aag ttc gag cag cat acc       2249
Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr           
            350                 355                 360                   

gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg atc atg gac agc       2297
Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser           
        365                 370                 375                       

ctg cat atg gcc gcc aga gag cag cag gtc tac tgc gag gaa atg cgg       2345
Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met Arg           
    380                 385                 390                           

gaa gag aga cag gac cgg ctg aag ttc atc gac aag cag ctg gaa ctg       2393
Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu           
395                 400                 405                 410           

ctg gcc cag gac tac aag ctg cgg atc aag cag atc acc gaa gag gtg       2441
Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu Val           
                415                 420                 425               

gaa aga cag gtg tcc acc gct atg gcc gag gaa atc aga cgg ctg agc       2489
Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser           
            430                 435                 440                   

gtg ctg gtc gac gac tac cag atg gac ttt cac ccc tct cca gtg gtg       2537
Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val Val           
        445                 450                 455                       

ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc gag gaa ggc ctg       2585
Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu           
    460                 465                 470                           

ggc aga aac atg agc gac aga tgc agc acc gcc atc acc aat agc ctg       2633
Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu           
475                 480                 485                 490           

cag acc atg cag cag gac atg atc gac ggc ctg aaa cct ctg ctg cct       2681
Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro           
                495                 500                 505               

gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc cgg cag tgc ttt       2729
Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe           
            510                 515                 520                   

agc ctg aac tac gac ctg aac tgc gac aag ctg tgc gcc gat ttc caa       2777
Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln           
        525                 530                 535                       

gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc aac       2825
Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn           
    540                 545                 550                           

aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg atg ggc tac aac       2873
Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn           
555                 560                 565                 570           

gat cag gtg cag agg ccc att cct ctg aca ccc gcc aat cct agc atg       2921
Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser Met           
                575                 580                 585               

cct cca ctg cct cag ggc agc ctg aca caa gag gaa ttc atg gtg tct       2969
Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val Ser           
            590                 595                 600                   

atg gtc acc ggc ctg gcc agc ctg acc agc aga aca tct atg ggc atc       3017
Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile           
        605                 610                 615                       

ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc tgg cgg ctg atc       3065
Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile           
    620                 625                 630                           

gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg tac gag aga ctg       3113
Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu           
635                 640                 645                 650           

acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag cgg cag ttt gtg       3161
Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val           
                655                 660                 665               

gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc tac acc ggc agc       3209
Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser           
            670                 675                 680                   

aat tgc agc cac cag gtg cag caa gag ctg tcc gga aca ttc gcc cac       3257
Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His           
        685                 690                 695                       

ctg tgt cag cag gtc gac gtg acc aga gag aac ctg gaa caa gag atc       3305
Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu Ile           
    700                 705                 710                           

gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc ctg cag agc aag       3353
Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser Lys           
715                 720                 725                 730           

gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac agc gag ctg aat       3401
Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn           
                735                 740                 745               

atg ttc acc cac cag tac ctg cag cct agc cgc taa taaagcggcc            3447
Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg                               
            750                 755                                       

gcaagcttgc acccgtacct ttgggagcgc gcgccctcgt cgtgtcgtga cgtcacccgt     3507

tctgttggat ccctggaggc ttgctgaagg ctgtatgctg ttcttataaa ccttgaggac     3567

agttttggcc actgactgac tgtcctcagt ttataagaac aggacacaag gcctgttact     3627

agcactcaca tggaacaaat ggcccagatc ttaagcttct cgagatcgat aatcaacctc     3687

tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct ccttttacgc     3747

tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt atggctttca     3807

ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg tggcccgttg     3867

tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact ggttggggca     3927

ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct attgccacgg     3987

cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg ttgggcactg     4047

acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg     4107

ccacctggat tctgcgcggg acgcccttct gctacgtccc ttcggccctc aatccagcgg     4167

accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc     4227

ctcagacgag tcggatctcc ctttgggccg cctccccgcc tgctgatcgc cctgagcctg     4287

gccctggtga ccaacagcca ggtgcaattg ctagagtcga ctctagagcg gccgcttcga     4347

gcagacatga taagatacat tgatgagttt ggacaaacca caactagaat gcagtgaaaa     4407

aaatgcttta tttgtgaaat ttgtgatgct attgctttat ttgtaaccat tataagctgc     4467

aataaacaag ttaacaacaa caattgcatt cattttatgt ttcaggttca gggggagatg     4527

tgggaggttt tttaaagcaa gtaaaacctc tacaaatgtg gtaaaatcga taaggatctt     4587

cctagagcat ggctacgtag ataagtagca tggcgggtta atcattaact acaaggaacc     4647

cctagtgatg gagttggcca ctccctctct gcgcgctcgc tcgctcactg aggccgggcg     4707

accaaaggtc gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg agcgagcgcg     4767

cagc                                                                  4771


<210>  72
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  72

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  73
<211>  4559
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector genome CAG.CI.hMfn2.GA.WPRE.SV40


<220>
<221>  repeat_region
<222>  (1)..(188)
<223>  ITR

<220>
<221>  misc_feature
<222>  (192)..(1032)
<223>  CAG (CBA)

<220>
<221>  enhancer
<222>  (194)..(1032)
<223>  CMV enhancer

<220>
<221>  promoter
<222>  (439)..(720)
<223>  CB promoter

<220>
<221>  Intron
<222>  (720)..(1127)
<223>  Hybrid intron in CAG

<220>
<221>  Intron
<222>  (720)..(950)
<223>  b-actin intron

<220>
<221>  misc_feature
<222>  (1158)..(1163)
<223>  Kozak

<220>
<221>  CDS
<222>  (1164)..(3437)
<223>  huamn Mfn2 engineered

<220>
<221>  misc_feature
<222>  (1379)..(1399)
<223>  miR538 mut

<220>
<221>  misc_feature
<222>  (2534)..(2554)
<223>  miR1518 mutated

<220>
<221>  misc_feature
<222>  (3466)..(4054)
<223>  WRPE

<220>
<221>  misc_feature
<222>  (4143)..(4262)
<223>  SV 40 PA temrinator

<220>
<221>  rep_origin
<222>  (4372)..(4559)
<223>  ITR

<400>  73
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacgt agccatgctc      180

taggaagagt accattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga      240

ctttccattg acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc      300

aagtgtatca tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct      360

ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat      420

tagtcatcgc tattaccatg gtcgaggtga gccccacgtt ctgcttcact ctccccatct      480

cccccccctc cccaccccca attttgtatt tatttatttt ttaattattt tgtgcagcga      540

tgggggcggg gggggggggg gggcgcgcgc caggcggggc ggggcggggc gaggggcggg      600

gcggggcgag gcggagaggt gcggcggcag ccaatcagag cggcgcgctc cgaaagtttc      660

cttttatggc gaggcggcgg cggcggcggc cctataaaaa gcgaagcgcg cggcgggcgg      720

gagtcgctgc gcgctgcctt cgccccgtgc cccgctccgc cgccgcctcg cgccgcccgc      780

cccggctctg actgaccgcg ttactcccac aggtgagcgg gcgggacggc ccttctcctc      840

cgggctgtaa ttagcgcttg gtttaatgac ggcttgtttc ttttctgtgg ctgcgtgaaa      900

gccttgaggg gctccgggag ggccctttgt gcggggggag cggctcgggg ctgtccgcgg      960

ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg gcgtgtgacc     1020

ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct acagctcctg     1080

ggcaacgtgc tggttattgt gctgtctcat cattttggca aagaattgga tcccgtacga     1140

cgcgtgctag caccggtgcc acc atg agc ctg ctg ttc agc cgg tgc aac agc     1193
                          Met Ser Leu Leu Phe Ser Arg Cys Asn Ser         
                          1               5                   10          

atc gtg acc gtg aag aaa aac aag cgg cac atg gcc gaa gtg aac gcc       1241
Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn Ala           
                15                  20                  25                

tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac ggc atc       1289
Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly Ile           
            30                  35                  40                    

ttc gag cag ctg ggc gcc tac atc caa gag agc gcc acc ttc ctg gaa       1337
Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu           
        45                  50                  55                        

gat acc tac aga aac gcc gag ctg gac ccc gtg acc aca gag gaa cag       1385
Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu Gln           
    60                  65                  70                            

gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg ggc atc tct gaa       1433
Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu           
75                  80                  85                  90            

gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc ggc cgg acc agc       1481
Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr Ser           
                95                  100                 105               

aac ggc aag agc acc gtg atc aat gcc atg ctg tgg gac aaa gtg ctg       1529
Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val Leu           
            110                 115                 120                   

ccc tct gga atc ggc cac acc acc aac tgc ttt ctg aga gtg gaa ggc       1577
Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu Gly           
        125                 130                 135                       

acc gac ggc cac gag gca ttt ctg ctg aca gag ggc tcc gag gaa aag       1625
Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys           
    140                 145                 150                           

cgg agc gcc aag aca gtg aac cag ctg gcc cat gct ctg cac cag gat       1673
Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln Asp           
155                 160                 165                 170           

aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg tgg ccc aat agc       1721
Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn Ser           
                175                 180                 185               

aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gat agc ccc ggg       1769
Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro Gly           
            190                 195                 200                   

atc gat gtg acc acc gaa ctg gac agc tgg atc gac aag ttc tgc ctg       1817
Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu           
        205                 210                 215                       

gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag agc acc ctg atg       1865
Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu Met           
    220                 225                 230                           

cag acc gag aag cac ttt ttc cac aag gtg tcc gag cgg ctg agc aga       1913
Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser Arg           
235                 240                 245                 250           

ccc aat atc ttt atc ctg aac aac aga tgg gac gcc agc gcc agc gag       1961
Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu           
                255                 260                 265               

ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg gaa cgg tgc aca       2009
Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys Thr           
            270                 275                 280                   

tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga tct cag gcc ggc       2057
Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala Gly           
        285                 290                 295                       

gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg aac gcc cgg att       2105
Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg Ile           
    300                 305                 310                           

cag aaa gcc cag gga atg cct gaa ggc gga ggt gca ctg gcc gag gga       2153
Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly           
315                 320                 325                 330           

ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc gag       2201
Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu           
                335                 340                 345               

gag tgc atc agc cag agc gcc gtc aag acc aag ttc gag cag cat acc       2249
Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His Thr           
            350                 355                 360                   

gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg atc atg gac agc       2297
Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp Ser           
        365                 370                 375                       

ctg cat atg gcc gcc aga gag cag cag gtc tac tgc gag gaa atg cgg       2345
Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met Arg           
    380                 385                 390                           

gaa gag aga cag gac cgg ctg aag ttc atc gac aag cag ctg gaa ctg       2393
Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu           
395                 400                 405                 410           

ctg gcc cag gac tac aag ctg cgg atc aag cag atc acc gaa gag gtg       2441
Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu Val           
                415                 420                 425               

gaa aga cag gtg tcc acc gct atg gcc gag gaa atc aga cgg ctg agc       2489
Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu Ser           
            430                 435                 440                   

gtg ctg gtc gac gac tac cag atg gac ttt cac ccc tct cca gtg gtg       2537
Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val Val           
        445                 450                 455                       

ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc gag gaa ggc ctg       2585
Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly Leu           
    460                 465                 470                           

ggc aga aac atg agc gac aga tgc agc acc gcc atc acc aat agc ctg       2633
Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu           
475                 480                 485                 490           

cag acc atg cag cag gac atg atc gac ggc ctg aaa cct ctg ctg cct       2681
Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu Pro           
                495                 500                 505               

gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc cgg cag tgc ttt       2729
Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys Phe           
            510                 515                 520                   

agc ctg aac tac gac ctg aac tgc gac aag ctg tgc gcc gat ttc caa       2777
Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln           
        525                 530                 535                       

gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc aac       2825
Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val Asn           
    540                 545                 550                           

aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg atg ggc tac aac       2873
Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn           
555                 560                 565                 570           

gat cag gtg cag agg ccc att cct ctg aca ccc gcc aat cct agc atg       2921
Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser Met           
                575                 580                 585               

cct cca ctg cct cag ggc agc ctg aca caa gag gaa ttc atg gtg tct       2969
Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val Ser           
            590                 595                 600                   

atg gtc acc ggc ctg gcc agc ctg acc agc aga aca tct atg ggc atc       3017
Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly Ile           
        605                 610                 615                       

ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc tgg cgg ctg atc       3065
Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu Ile           
    620                 625                 630                           

gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg tac gag aga ctg       3113
Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu           
635                 640                 645                 650           

acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag cgg cag ttt gtg       3161
Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe Val           
                655                 660                 665               

gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc tac acc ggc agc       3209
Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser           
            670                 675                 680                   

aat tgc agc cac cag gtg cag caa gag ctg tcc gga aca ttc gcc cac       3257
Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala His           
        685                 690                 695                       

ctg tgt cag cag gtc gac gtg acc aga gag aac ctg gaa caa gag atc       3305
Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu Ile           
    700                 705                 710                           

gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc ctg cag agc aag       3353
Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser Lys           
715                 720                 725                 730           

gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac agc gag ctg aat       3401
Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn           
                735                 740                 745               

atg ttc acc cac cag tac ctg cag cct agc cgc taa taatgtactt            3447
Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg                               
            750                 755                                       

aagcttctcg agatcgataa tcaacctctg gattacaaaa tttgtgaaag attgactggt     3507

attcttaact atgttgctcc ttttacgcta tgtggatacg ctgctttaat gcctttgtat     3567

catgctattg cttcccgtat ggctttcatt ttctcctcct tgtataaatc ctggttgctg     3627

tctctttatg aggagttgtg gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt     3687

gctgacgcaa cccccactgg ttggggcatt gccaccacct gtcagctcct ttccgggact     3747

ttcgctttcc ccctccctat tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc     3807

tggacagggg ctcggctgtt gggcactgac aattccgtgg tgttgtcggg gaaatcatcg     3867

tcctttcctt ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gcccttctgc     3927

tacgtccctt cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg     3987

cggcctcttc cgcgtcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc     4047

tccccgcctg ctgatcgccc tgagcctggc cctggtgacc aacagccagg tgcaattgct     4107

agagtcgact ctagagcggc cgcttcgagc agacatgata agatacattg atgagtttgg     4167

acaaaccaca actagaatgc agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat     4227

tgctttattt gtaaccatta taagctgcaa taaacaagtt aacaacaaca attgcattca     4287

ttttatgttt caggttcagg gggagatgtg ggaggttttt taaagcaagt aaaacctcta     4347

caaatgtggt aaaatcgata aggatcttcc tagagcatgg ctacgtagat aagtagcatg     4407

gcgggttaat cattaactac aaggaacccc tagtgatgga gttggccact ccctctctgc     4467

gcgctcgctc gctcactgag gccgggcgac caaaggtcgc ccgacgcccg ggctttgccc     4527

gggcggcctc agtgagcgag cgagcgcgca gc                                   4559


<210>  74
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  74

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  75
<211>  4821
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector genome CB7.CI.hMfn2.GA.link.miR538.rBG


<220>
<221>  repeat_region
<222>  (1)..(130)
<223>  ITR

<220>
<221>  enhancer
<222>  (259)..(562)
<223>  CMV enhancer

<220>
<221>  promoter
<222>  (561)..(842)
<223>  CB7 promoter

<220>
<221>  Intron
<222>  (935)..(1907)
<223>  chicken beta-actin intron

<220>
<221>  misc_feature
<222>  (1953)..(1958)
<223>  Kozak

<220>
<221>  CDS
<222>  (1959)..(4232)
<223>  human Mfn2 engineered

<220>
<221>  misc_feature
<222>  (2174)..(2194)
<223>  miR538 mut

<220>
<221>  misc_feature
<222>  (3329)..(3349)
<223>  miR1518

<220>
<221>  misc_feature
<222>  (4233)..(4314)
<223>  linker p5271

<220>
<221>  misc_feature
<222>  (4315)..(4342)
<223>  5' flank

<220>
<221>  misc_feature
<222>  (4343)..(4363)
<223>  miR538 AS

<220>
<221>  misc_feature
<222>  (4364)..(4382)
<223>  loop

<220>
<221>  misc_feature
<222>  (4383)..(4401)
<223>  miR538 Sense

<220>
<221>  misc_feature
<222>  (4402)..(4446)
<223>  3' flank

<220>
<221>  polyA_signal
<222>  (4500)..(4626)
<223>  rabbit globin poly A

<220>
<221>  repeat_region
<222>  (4692)..(4821)
<223>  ITR

<400>  75
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctacgta gccatgctct      180

aggaagatct gatatcacta gttattaata gtaatcaatt acggggtcat tagttcatag      240

cccatatatg gagttccgcg ttacataact tacggtaaat ggcccgcctg gctgaccgcc      300

caacgacccc cgcccattga cgtcaataat gacgtatgtt cccatagtaa cgccaatagg      360

gactttccat tgacgtcaat gggtggagta tttacggtaa actgcccact tggcagtaca      420

tcaagtgtat catatgccaa gtacgccccc tattgacgtc aatgacggta aatggcccgc      480

ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt acatctacgt      540

attagtcatc gctattacca tggtcgaggt gagccccacg ttctgcttca ctctccccat      600

ctcccccccc tccccacccc caattttgta tttatttatt ttttaattat tttgtgcagc      660

gatgggggcg gggggggggg gggggcgcgc gccaggcggg gcggggcggg gcgaggggcg      720

gggcggggcg aggcggagag gtgcggcggc agccaatcag agcggcgcgc tccgaaagtt      780

tccttttatg gcgaggcggc ggcggcggcg gccctataaa aagcgaagcg cgcggcgggc      840

gggagtcgct gcgcgctgcc ttcgccccgt gccccgctcc gccgccgcct cgcgccgccc      900

gccccggctc tgactgaccg cgttactccc acaggtgagc gggcgggacg gcccttctcc      960

tccgggctgt aattagcgct tggtttaatg acggcttgtt tcttttctgt ggctgcgtga     1020

aagccttgag gggctccggg agggcccttt gtgcgggggg agcggctcgg ggggtgcgtg     1080

cgtgtgtgtg tgcgtgggga gcgccgcgtg cggctccgcg ctgcccggcg gctgtgagcg     1140

ctgcgggcgc ggcgcggggc tttgtgcgct ccgcagtgtg cgcgagggga gcgcggccgg     1200

gggcggtgcc ccgcggtgcg gggggggctg cgaggggaac aaaggctgcg tgcggggtgt     1260

gtgcgtgggg gggtgagcag ggggtgtggg cgcgtcggtc gggctgcaac cccccctgca     1320

cccccctccc cgagttgctg agcacggccc ggcttcgggt gcggggctcc gtacggggcg     1380

tggcgcgggg ctcgccgtgc cgggcggggg gtggcggcag gtgggggtgc cgggcggggc     1440

ggggccgcct cgggccgggg agggctcggg ggaggggcgc ggcggccccc ggagcgccgg     1500

cggctgtcga ggcgcggcga gccgcagcca ttgcctttta tggtaatcgt gcgagagggc     1560

gcagggactt cctttgtccc aaatctgtgc ggagccgaaa tctgggaggc gccgccgcac     1620

cccctctagc gggcgcgggg cgaagcggtg cggcgccggc aggaaggaaa tgggcgggga     1680

gggccttcgt gcgtcgccgc gccgccgtcc ccttctccct ctccagcctc ggggctgtcc     1740

gcggggggac ggctgccttc gggggggacg gggcagggcg gggttcggct tctggcgtgt     1800

gaccggcggc tctagagcct ctgctaacca tgttcatgcc ttcttctttt tcctacagct     1860

cctgggcaac gtgctggtta ttgtgctgtc tcatcatttt ggcaaagaat tcacgcgtgc     1920

taggatcccg tacgacgcgt gctagcaccg gtgccacc atg agc ctg ctg ttc agc     1976
                                          Met Ser Leu Leu Phe Ser         
                                          1               5               

cgg tgc aac agc atc gtg acc gtg aag aaa aac aag cgg cac atg gcc       2024
Arg Cys Asn Ser Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala           
            10                  15                  20                    

gaa gtg aac gcc tct cca ctg aag cac ttc gtg acc gcc aag aag aag       2072
Glu Val Asn Ala Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys           
        25                  30                  35                        

atc aac ggc atc ttc gag cag ctg ggc gcc tac atc caa gag agc gcc       2120
Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala           
    40                  45                  50                            

acc ttc ctg gaa gat acc tac aga aac gcc gag ctg gac ccc gtg acc       2168
Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr           
55                  60                  65                  70            

aca gag gaa cag gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg       2216
Thr Glu Glu Gln Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg           
                75                  80                  85                

ggc atc tct gaa gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc       2264
Gly Ile Ser Glu Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe           
            90                  95                  100                   

ggc cgg acc agc aac ggc aag agc acc gtg atc aat gcc atg ctg tgg       2312
Gly Arg Thr Ser Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp           
        105                 110                 115                       

gac aaa gtg ctg ccc tct gga atc ggc cac acc acc aac tgc ttt ctg       2360
Asp Lys Val Leu Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu           
    120                 125                 130                           

aga gtg gaa ggc acc gac ggc cac gag gca ttt ctg ctg aca gag ggc       2408
Arg Val Glu Gly Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly           
135                 140                 145                 150           

tcc gag gaa aag cgg agc gcc aag aca gtg aac cag ctg gcc cat gct       2456
Ser Glu Glu Lys Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala           
                155                 160                 165               

ctg cac cag gat aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg       2504
Leu His Gln Asp Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met           
            170                 175                 180                   

tgg ccc aat agc aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg       2552
Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met           
        185                 190                 195                       

gat agc ccc ggg atc gat gtg acc acc gaa ctg gac agc tgg atc gac       2600
Asp Ser Pro Gly Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp           
    200                 205                 210                           

aag ttc tgc ctg gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag       2648
Lys Phe Cys Leu Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu           
215                 220                 225                 230           

agc acc ctg atg cag acc gag aag cac ttt ttc cac aag gtg tcc gag       2696
Ser Thr Leu Met Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu           
                235                 240                 245               

cgg ctg agc aga ccc aat atc ttt atc ctg aac aac aga tgg gac gcc       2744
Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala           
            250                 255                 260                   

agc gcc agc gag ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg       2792
Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met           
        265                 270                 275                       

gaa cgg tgc aca tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga       2840
Glu Arg Cys Thr Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg           
    280                 285                 290                           

tct cag gcc ggc gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg       2888
Ser Gln Ala Gly Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu           
295                 300                 305                 310           

aac gcc cgg att cag aaa gcc cag gga atg cct gaa ggc gga ggt gca       2936
Asn Ala Arg Ile Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala           
                315                 320                 325               

ctg gcc gag gga ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag       2984
Leu Ala Glu Gly Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu           
            330                 335                 340                   

cgg aga ttc gag gag tgc atc agc cag agc gcc gtc aag acc aag ttc       3032
Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe           
        345                 350                 355                       

gag cag cat acc gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg       3080
Glu Gln His Thr Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu           
    360                 365                 370                           

atc atg gac agc ctg cat atg gcc gcc aga gag cag cag gtc tac tgc       3128
Ile Met Asp Ser Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys           
375                 380                 385                 390           

gag gaa atg cgg gaa gag aga cag gac cgg ctg aag ttc atc gac aag       3176
Glu Glu Met Arg Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys           
                395                 400                 405               

cag ctg gaa ctg ctg gcc cag gac tac aag ctg cgg atc aag cag atc       3224
Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile           
            410                 415                 420                   

acc gaa gag gtg gaa aga cag gtg tcc acc gct atg gcc gag gaa atc       3272
Thr Glu Glu Val Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile           
        425                 430                 435                       

aga cgg ctg agc gtg ctg gtc gac gac tac cag atg gac ttt cac ccc       3320
Arg Arg Leu Ser Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro           
    440                 445                 450                           

tct cca gtg gtg ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc       3368
Ser Pro Val Val Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile           
455                 460                 465                 470           

gag gaa ggc ctg ggc aga aac atg agc gac aga tgc agc acc gcc atc       3416
Glu Glu Gly Leu Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile           
                475                 480                 485               

acc aat agc ctg cag acc atg cag cag gac atg atc gac ggc ctg aaa       3464
Thr Asn Ser Leu Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys           
            490                 495                 500                   

cct ctg ctg cct gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc       3512
Pro Leu Leu Pro Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro           
        505                 510                 515                       

cgg cag tgc ttt agc ctg aac tac gac ctg aac tgc gac aag ctg tgc       3560
Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys           
    520                 525                 530                           

gcc gat ttc caa gag gac atc gag ttt cac ttc agc ctc ggc tgg aca       3608
Ala Asp Phe Gln Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr           
535                 540                 545                 550           

atg ctg gtc aac aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg       3656
Met Leu Val Asn Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu           
                555                 560                 565               

atg ggc tac aac gat cag gtg cag agg ccc att cct ctg aca ccc gcc       3704
Met Gly Tyr Asn Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala           
            570                 575                 580                   

aat cct agc atg cct cca ctg cct cag ggc agc ctg aca caa gag gaa       3752
Asn Pro Ser Met Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu           
        585                 590                 595                       

ttc atg gtg tct atg gtc acc ggc ctg gcc agc ctg acc agc aga aca       3800
Phe Met Val Ser Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr           
    600                 605                 610                           

tct atg ggc atc ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc       3848
Ser Met Gly Ile Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly           
615                 620                 625                 630           

tgg cgg ctg atc gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg       3896
Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val           
                635                 640                 645               

tac gag aga ctg acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag       3944
Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys           
            650                 655                 660                   

cgg cag ttt gtg gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc       3992
Arg Gln Phe Val Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser           
        665                 670                 675                       

tac acc ggc agc aat tgc agc cac cag gtg cag caa gag ctg tcc gga       4040
Tyr Thr Gly Ser Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly           
    680                 685                 690                           

aca ttc gcc cac ctg tgt cag cag gtc gac gtg acc aga gag aac ctg       4088
Thr Phe Ala His Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu           
695                 700                 705                 710           

gaa caa gag atc gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc       4136
Glu Gln Glu Ile Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser           
                715                 720                 725               

ctg cag agc aag gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac       4184
Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp           
            730                 735                 740                   

agc gag ctg aat atg ttc acc cac cag tac ctg cag cct agc cgc taa       4232
Ser Glu Leu Asn Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg               
        745                 750                 755                       

taaagcggcc gcaagcttgc acccgtacct ttgggagcgc gcgccctcgt cgtgtcgtga     4292

cgtcacccgt tctgttggat ccctggaggc ttgctgaagg ctgtatgctg ttgacgtcca     4352

gaacctgttc tgttttggcc actgactgac agaacaggct ggacgtcaac aggacacaag     4412

gcctgttact agcactcaca tggaacaaat ggcccagatc agctttctag agtcgacccg     4472

ggcggcggcg gccgcctaag gctcgaggat ctttttccct ctgccaaaaa ttatggggac     4532

atcatgaagc cccttgagca tctgacttct ggctaataaa ggaaatttat tttcattgca     4592

atagtgtgtt ggaatttttt gtgtctctca ctcggataag gatcttccta gagcatggct     4652

acgtagataa gtagcatggc gggttaatca ttaactacaa ggaaccccta gtgatggagt     4712

tggccactcc ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca aaggtcgccc     4772

gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg agcgcgcag                 4821


<210>  76
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  76

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  77
<211>  4905
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector genome CB7.CI.hMfn2.GA.link.miR1518.rBG


<220>
<221>  repeat_region
<222>  (1)..(130)
<223>  ITR

<220>
<221>  enhancer
<222>  (259)..(562)
<223>  CMV enhancer

<220>
<221>  promoter
<222>  (561)..(842)
<223>  CB7 promoter

<220>
<221>  Intron
<222>  (935)..(1907)
<223>  chicken beta-actin intron

<220>
<221>  misc_feature
<222>  (1953)..(1958)
<223>  Kozak

<220>
<221>  CDS
<222>  (1959)..(4232)
<223>  human Mfn2 engineered

<220>
<221>  misc_feature
<222>  (2174)..(2194)
<223>  miR538 mut

<220>
<221>  misc_feature
<222>  (3329)..(3349)
<223>  miR 1518 mutated

<220>
<221>  misc_feature
<222>  (4233)..(4314)
<223>  linker p4271

<220>
<221>  misc_feature
<222>  (4315)..(4342)
<223>  5' flank

<220>
<221>  misc_feature
<222>  (4343)..(4363)
<223>  rat miR1518 AS

<220>
<221>  misc_feature
<222>  (4364)..(4382)
<223>  loop

<220>
<221>  misc_feature
<222>  (4383)..(4401)
<223>  rat miR 1518 sense

<220>
<221>  misc_feature
<222>  (4402)..(4446)
<223>  3'Flank

<220>
<221>  polyA_signal
<222>  (4584)..(4710)
<223>  rabbit globin polyA

<220>
<221>  repeat_region
<222>  (4776)..(4905)
<223>  ITR

<400>  77
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctacgta gccatgctct      180

aggaagatct gatatcacta gttattaata gtaatcaatt acggggtcat tagttcatag      240

cccatatatg gagttccgcg ttacataact tacggtaaat ggcccgcctg gctgaccgcc      300

caacgacccc cgcccattga cgtcaataat gacgtatgtt cccatagtaa cgccaatagg      360

gactttccat tgacgtcaat gggtggagta tttacggtaa actgcccact tggcagtaca      420

tcaagtgtat catatgccaa gtacgccccc tattgacgtc aatgacggta aatggcccgc      480

ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt acatctacgt      540

attagtcatc gctattacca tggtcgaggt gagccccacg ttctgcttca ctctccccat      600

ctcccccccc tccccacccc caattttgta tttatttatt ttttaattat tttgtgcagc      660

gatgggggcg gggggggggg gggggcgcgc gccaggcggg gcggggcggg gcgaggggcg      720

gggcggggcg aggcggagag gtgcggcggc agccaatcag agcggcgcgc tccgaaagtt      780

tccttttatg gcgaggcggc ggcggcggcg gccctataaa aagcgaagcg cgcggcgggc      840

gggagtcgct gcgcgctgcc ttcgccccgt gccccgctcc gccgccgcct cgcgccgccc      900

gccccggctc tgactgaccg cgttactccc acaggtgagc gggcgggacg gcccttctcc      960

tccgggctgt aattagcgct tggtttaatg acggcttgtt tcttttctgt ggctgcgtga     1020

aagccttgag gggctccggg agggcccttt gtgcgggggg agcggctcgg ggggtgcgtg     1080

cgtgtgtgtg tgcgtgggga gcgccgcgtg cggctccgcg ctgcccggcg gctgtgagcg     1140

ctgcgggcgc ggcgcggggc tttgtgcgct ccgcagtgtg cgcgagggga gcgcggccgg     1200

gggcggtgcc ccgcggtgcg gggggggctg cgaggggaac aaaggctgcg tgcggggtgt     1260

gtgcgtgggg gggtgagcag ggggtgtggg cgcgtcggtc gggctgcaac cccccctgca     1320

cccccctccc cgagttgctg agcacggccc ggcttcgggt gcggggctcc gtacggggcg     1380

tggcgcgggg ctcgccgtgc cgggcggggg gtggcggcag gtgggggtgc cgggcggggc     1440

ggggccgcct cgggccgggg agggctcggg ggaggggcgc ggcggccccc ggagcgccgg     1500

cggctgtcga ggcgcggcga gccgcagcca ttgcctttta tggtaatcgt gcgagagggc     1560

gcagggactt cctttgtccc aaatctgtgc ggagccgaaa tctgggaggc gccgccgcac     1620

cccctctagc gggcgcgggg cgaagcggtg cggcgccggc aggaaggaaa tgggcgggga     1680

gggccttcgt gcgtcgccgc gccgccgtcc ccttctccct ctccagcctc ggggctgtcc     1740

gcggggggac ggctgccttc gggggggacg gggcagggcg gggttcggct tctggcgtgt     1800

gaccggcggc tctagagcct ctgctaacca tgttcatgcc ttcttctttt tcctacagct     1860

cctgggcaac gtgctggtta ttgtgctgtc tcatcatttt ggcaaagaat tcacgcgtgc     1920

taggatcccg tacgacgcgt gctagcaccg gtgccacc atg agc ctg ctg ttc agc     1976
                                          Met Ser Leu Leu Phe Ser         
                                          1               5               

cgg tgc aac agc atc gtg acc gtg aag aaa aac aag cgg cac atg gcc       2024
Arg Cys Asn Ser Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala           
            10                  15                  20                    

gaa gtg aac gcc tct cca ctg aag cac ttc gtg acc gcc aag aag aag       2072
Glu Val Asn Ala Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys           
        25                  30                  35                        

atc aac ggc atc ttc gag cag ctg ggc gcc tac atc caa gag agc gcc       2120
Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala           
    40                  45                  50                            

acc ttc ctg gaa gat acc tac aga aac gcc gag ctg gac ccc gtg acc       2168
Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr           
55                  60                  65                  70            

aca gag gaa cag gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg       2216
Thr Glu Glu Gln Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg           
                75                  80                  85                

ggc atc tct gaa gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc       2264
Gly Ile Ser Glu Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe           
            90                  95                  100                   

ggc cgg acc agc aac ggc aag agc acc gtg atc aat gcc atg ctg tgg       2312
Gly Arg Thr Ser Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp           
        105                 110                 115                       

gac aaa gtg ctg ccc tct gga atc ggc cac acc acc aac tgc ttt ctg       2360
Asp Lys Val Leu Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu           
    120                 125                 130                           

aga gtg gaa ggc acc gac ggc cac gag gca ttt ctg ctg aca gag ggc       2408
Arg Val Glu Gly Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly           
135                 140                 145                 150           

tcc gag gaa aag cgg agc gcc aag aca gtg aac cag ctg gcc cat gct       2456
Ser Glu Glu Lys Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala           
                155                 160                 165               

ctg cac cag gat aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg       2504
Leu His Gln Asp Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met           
            170                 175                 180                   

tgg ccc aat agc aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg       2552
Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met           
        185                 190                 195                       

gat agc ccc ggg atc gat gtg acc acc gaa ctg gac agc tgg atc gac       2600
Asp Ser Pro Gly Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp           
    200                 205                 210                           

aag ttc tgc ctg gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag       2648
Lys Phe Cys Leu Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu           
215                 220                 225                 230           

agc acc ctg atg cag acc gag aag cac ttt ttc cac aag gtg tcc gag       2696
Ser Thr Leu Met Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu           
                235                 240                 245               

cgg ctg agc aga ccc aat atc ttt atc ctg aac aac aga tgg gac gcc       2744
Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala           
            250                 255                 260                   

agc gcc agc gag ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg       2792
Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met           
        265                 270                 275                       

gaa cgg tgc aca tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga       2840
Glu Arg Cys Thr Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg           
    280                 285                 290                           

tct cag gcc ggc gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg       2888
Ser Gln Ala Gly Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu           
295                 300                 305                 310           

aac gcc cgg att cag aaa gcc cag gga atg cct gaa ggc gga ggt gca       2936
Asn Ala Arg Ile Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala           
                315                 320                 325               

ctg gcc gag gga ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag       2984
Leu Ala Glu Gly Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu           
            330                 335                 340                   

cgg aga ttc gag gag tgc atc agc cag agc gcc gtc aag acc aag ttc       3032
Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe           
        345                 350                 355                       

gag cag cat acc gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg       3080
Glu Gln His Thr Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu           
    360                 365                 370                           

atc atg gac agc ctg cat atg gcc gcc aga gag cag cag gtc tac tgc       3128
Ile Met Asp Ser Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys           
375                 380                 385                 390           

gag gaa atg cgg gaa gag aga cag gac cgg ctg aag ttc atc gac aag       3176
Glu Glu Met Arg Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys           
                395                 400                 405               

cag ctg gaa ctg ctg gcc cag gac tac aag ctg cgg atc aag cag atc       3224
Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile           
            410                 415                 420                   

acc gaa gag gtg gaa aga cag gtg tcc acc gct atg gcc gag gaa atc       3272
Thr Glu Glu Val Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile           
        425                 430                 435                       

aga cgg ctg agc gtg ctg gtc gac gac tac cag atg gac ttt cac ccc       3320
Arg Arg Leu Ser Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro           
    440                 445                 450                           

tct cca gtg gtg ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc       3368
Ser Pro Val Val Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile           
455                 460                 465                 470           

gag gaa ggc ctg ggc aga aac atg agc gac aga tgc agc acc gcc atc       3416
Glu Glu Gly Leu Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile           
                475                 480                 485               

acc aat agc ctg cag acc atg cag cag gac atg atc gac ggc ctg aaa       3464
Thr Asn Ser Leu Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys           
            490                 495                 500                   

cct ctg ctg cct gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc       3512
Pro Leu Leu Pro Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro           
        505                 510                 515                       

cgg cag tgc ttt agc ctg aac tac gac ctg aac tgc gac aag ctg tgc       3560
Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys           
    520                 525                 530                           

gcc gat ttc caa gag gac atc gag ttt cac ttc agc ctc ggc tgg aca       3608
Ala Asp Phe Gln Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr           
535                 540                 545                 550           

atg ctg gtc aac aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg       3656
Met Leu Val Asn Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu           
                555                 560                 565               

atg ggc tac aac gat cag gtg cag agg ccc att cct ctg aca ccc gcc       3704
Met Gly Tyr Asn Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala           
            570                 575                 580                   

aat cct agc atg cct cca ctg cct cag ggc agc ctg aca caa gag gaa       3752
Asn Pro Ser Met Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu           
        585                 590                 595                       

ttc atg gtg tct atg gtc acc ggc ctg gcc agc ctg acc agc aga aca       3800
Phe Met Val Ser Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr           
    600                 605                 610                           

tct atg ggc atc ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc       3848
Ser Met Gly Ile Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly           
615                 620                 625                 630           

tgg cgg ctg atc gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg       3896
Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val           
                635                 640                 645               

tac gag aga ctg acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag       3944
Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys           
            650                 655                 660                   

cgg cag ttt gtg gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc       3992
Arg Gln Phe Val Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser           
        665                 670                 675                       

tac acc ggc agc aat tgc agc cac cag gtg cag caa gag ctg tcc gga       4040
Tyr Thr Gly Ser Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly           
    680                 685                 690                           

aca ttc gcc cac ctg tgt cag cag gtc gac gtg acc aga gag aac ctg       4088
Thr Phe Ala His Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu           
695                 700                 705                 710           

gaa caa gag atc gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc       4136
Glu Gln Glu Ile Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser           
                715                 720                 725               

ctg cag agc aag gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac       4184
Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp           
            730                 735                 740                   

agc gag ctg aat atg ttc acc cac cag tac ctg cag cct agc cgc taa       4232
Ser Glu Leu Asn Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg               
        745                 750                 755                       

taaagcggcc gcaagcttgc acccgtacct ttgggagcgc gcgccctcgt cgtgtcgtga     4292

cgtcacccgt tctgttggat ccctggaggc ttgctgaagg ctgtatgctg ttcttataaa     4352

ccttgaggac agttttggcc actgactgac tgtcctcagt ttataagaac aggacacaag     4412

gcctgttact agcactcaca tggaacaaat ggcccagatc tagggtgggg ccacctgccg     4472

gtaggtgtgc ggtaggcttt tctccgtcgc aggacgcagg gttcgggcct agagcttatc     4532

gttaagcttt ctagagtcga cccgggcggc ggcggccgcc taaggctcga ggatcttttt     4592

ccctctgcca aaaattatgg ggacatcatg aagccccttg agcatctgac ttctggctaa     4652

taaaggaaat ttattttcat tgcaatagtg tgttggaatt ttttgtgtct ctcactcgga     4712

taaggatctt cctagagcat ggctacgtag ataagtagca tggcgggtta atcattaact     4772

acaaggaacc cctagtgatg gagttggcca ctccctctct gcgcgctcgc tcgctcactg     4832

aggccgggcg accaaaggtc gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg     4892

agcgagcgcg cag                                                        4905


<210>  78
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  78

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  79
<211>  4565
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector genome CB7.CI.hMfn2.GA.rBG


<220>
<221>  rep_origin
<222>  (1)..(130)
<223>  ITR

<220>
<221>  enhancer
<222>  (259)..(562)
<223>  CMV enhancer

<220>
<221>  promoter
<222>  (561)..(842)
<223>  CB7 promoter

<220>
<221>  TATA_signal
<222>  (815)..(818)
<223>  TATA signal

<220>
<221>  Intron
<222>  (935)..(1907)
<223>  Chicken beta-actin intron

<220>
<221>  misc_feature
<222>  (1940)..(1948)
<223>  Kozak

<220>
<221>  CDS
<222>  (1946)..(4219)
<223>  huamn Mfn2 engineered

<220>
<221>  misc_feature
<222>  (2161)..(2181)
<223>  miR538 mut

<220>
<221>  misc_feature
<222>  (3316)..(3336)
<223>  miR1518 mutated

<220>
<221>  polyA_signal
<222>  (4244)..(4370)
<223>  rabbit globin polyA

<220>
<221>  repeat_region
<222>  (4436)..(4565)
<223>  ITR

<400>  79
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctacgta gccatgctct      180

aggaagatct gatatcacta gttattaata gtaatcaatt acggggtcat tagttcatag      240

cccatatatg gagttccgcg ttacataact tacggtaaat ggcccgcctg gctgaccgcc      300

caacgacccc cgcccattga cgtcaataat gacgtatgtt cccatagtaa cgccaatagg      360

gactttccat tgacgtcaat gggtggagta tttacggtaa actgcccact tggcagtaca      420

tcaagtgtat catatgccaa gtacgccccc tattgacgtc aatgacggta aatggcccgc      480

ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt acatctacgt      540

attagtcatc gctattacca tggtcgaggt gagccccacg ttctgcttca ctctccccat      600

ctcccccccc tccccacccc caattttgta tttatttatt ttttaattat tttgtgcagc      660

gatgggggcg gggggggggg gggggcgcgc gccaggcggg gcggggcggg gcgaggggcg      720

gggcggggcg aggcggagag gtgcggcggc agccaatcag agcggcgcgc tccgaaagtt      780

tccttttatg gcgaggcggc ggcggcggcg gccctataaa aagcgaagcg cgcggcgggc      840

gggagtcgct gcgcgctgcc ttcgccccgt gccccgctcc gccgccgcct cgcgccgccc      900

gccccggctc tgactgaccg cgttactccc acaggtgagc gggcgggacg gcccttctcc      960

tccgggctgt aattagcgct tggtttaatg acggcttgtt tcttttctgt ggctgcgtga     1020

aagccttgag gggctccggg agggcccttt gtgcgggggg agcggctcgg ggggtgcgtg     1080

cgtgtgtgtg tgcgtgggga gcgccgcgtg cggctccgcg ctgcccggcg gctgtgagcg     1140

ctgcgggcgc ggcgcggggc tttgtgcgct ccgcagtgtg cgcgagggga gcgcggccgg     1200

gggcggtgcc ccgcggtgcg gggggggctg cgaggggaac aaaggctgcg tgcggggtgt     1260

gtgcgtgggg gggtgagcag ggggtgtggg cgcgtcggtc gggctgcaac cccccctgca     1320

cccccctccc cgagttgctg agcacggccc ggcttcgggt gcggggctcc gtacggggcg     1380

tggcgcgggg ctcgccgtgc cgggcggggg gtggcggcag gtgggggtgc cgggcggggc     1440

ggggccgcct cgggccgggg agggctcggg ggaggggcgc ggcggccccc ggagcgccgg     1500

cggctgtcga ggcgcggcga gccgcagcca ttgcctttta tggtaatcgt gcgagagggc     1560

gcagggactt cctttgtccc aaatctgtgc ggagccgaaa tctgggaggc gccgccgcac     1620

cccctctagc gggcgcgggg cgaagcggtg cggcgccggc aggaaggaaa tgggcgggga     1680

gggccttcgt gcgtcgccgc gccgccgtcc ccttctccct ctccagcctc ggggctgtcc     1740

gcggggggac ggctgccttc gggggggacg gggcagggcg gggttcggct tctggcgtgt     1800

gaccggcggc tctagagcct ctgctaacca tgttcatgcc ttcttctttt tcctacagct     1860

cctgggcaac gtgctggtta ttgtgctgtc tcatcatttt ggcaaagaat tcacgcgtgc     1920

tagcaaggat ccaccggtcg ccacc atg agc ctg ctg ttc agc cgg tgc aac       1972
                            Met Ser Leu Leu Phe Ser Arg Cys Asn           
                            1               5                             

agc atc gtg acc gtg aag aaa aac aag cgg cac atg gcc gaa gtg aac       2020
Ser Ile Val Thr Val Lys Lys Asn Lys Arg His Met Ala Glu Val Asn           
10                  15                  20                  25            

gcc tct cca ctg aag cac ttc gtg acc gcc aag aag aag atc aac gga       2068
Ala Ser Pro Leu Lys His Phe Val Thr Ala Lys Lys Lys Ile Asn Gly           
                30                  35                  40                

atc ttc gag cag ctg ggc gcc tac atc caa gag agc gcc acc ttc ctg       2116
Ile Phe Glu Gln Leu Gly Ala Tyr Ile Gln Glu Ser Ala Thr Phe Leu           
            45                  50                  55                    

gaa gat acc tac aga aac gcc gag ctg gac ccc gtg acc aca gag gaa       2164
Glu Asp Thr Tyr Arg Asn Ala Glu Leu Asp Pro Val Thr Thr Glu Glu           
        60                  65                  70                        

cag gtg ctg gat gtg aag ggc tac ctg agc aaa gtg cgg ggc atc tct       2212
Gln Val Leu Asp Val Lys Gly Tyr Leu Ser Lys Val Arg Gly Ile Ser           
    75                  80                  85                            

gaa gtg ctg gcc aga cgg cat atg aag gtg gcc ttt ttc ggc cgg acc       2260
Glu Val Leu Ala Arg Arg His Met Lys Val Ala Phe Phe Gly Arg Thr           
90                  95                  100                 105           

agc aac ggc aag agc acc gtg atc aat gcc atg ctg tgg gac aaa gtg       2308
Ser Asn Gly Lys Ser Thr Val Ile Asn Ala Met Leu Trp Asp Lys Val           
                110                 115                 120               

ctg ccc tct gga atc ggc cac acc acc aac tgc ttt ctg aga gtg gaa       2356
Leu Pro Ser Gly Ile Gly His Thr Thr Asn Cys Phe Leu Arg Val Glu           
            125                 130                 135                   

ggc acc gac ggc cac gag gca ttt ctg ctg aca gag ggc tcc gag gaa       2404
Gly Thr Asp Gly His Glu Ala Phe Leu Leu Thr Glu Gly Ser Glu Glu           
        140                 145                 150                       

aag cgg agc gcc aag aca gtg aac cag ctg gcc cat gct ctg cac cag       2452
Lys Arg Ser Ala Lys Thr Val Asn Gln Leu Ala His Ala Leu His Gln           
    155                 160                 165                           

gat aag cag ctg cat gcc gga agc ctg gtg tcc gtg atg tgg ccc aat       2500
Asp Lys Gln Leu His Ala Gly Ser Leu Val Ser Val Met Trp Pro Asn           
170                 175                 180                 185           

agc aag tgc cct ctg ctg aag gac gac ctg gtg ctg atg gat agc ccc       2548
Ser Lys Cys Pro Leu Leu Lys Asp Asp Leu Val Leu Met Asp Ser Pro           
                190                 195                 200               

ggg atc gat gtg acc acc gaa ctg gac agc tgg atc gac aag ttc tgc       2596
Gly Ile Asp Val Thr Thr Glu Leu Asp Ser Trp Ile Asp Lys Phe Cys           
            205                 210                 215                   

ctg gac gcc gac gtg ttc gtg ctg gtg gcc aat agc gag agc acc ctg       2644
Leu Asp Ala Asp Val Phe Val Leu Val Ala Asn Ser Glu Ser Thr Leu           
        220                 225                 230                       

atg cag acc gag aag cac ttt ttc cac aag gtg tcc gag cgg ctg agc       2692
Met Gln Thr Glu Lys His Phe Phe His Lys Val Ser Glu Arg Leu Ser           
    235                 240                 245                           

aga ccc aat atc ttt atc ctg aac aac aga tgg gac gcc agc gcc agc       2740
Arg Pro Asn Ile Phe Ile Leu Asn Asn Arg Trp Asp Ala Ser Ala Ser           
250                 255                 260                 265           

gag ccc gag tat atg gaa gaa gtg cgg cgg cag cat atg gaa cgg tgc       2788
Glu Pro Glu Tyr Met Glu Glu Val Arg Arg Gln His Met Glu Arg Cys           
                270                 275                 280               

aca tcc ttt ctg gtg gac gag ctg ggc gtc gtg gat aga tct cag gcc       2836
Thr Ser Phe Leu Val Asp Glu Leu Gly Val Val Asp Arg Ser Gln Ala           
            285                 290                 295                   

ggc gac aga atc ttc ttt gtg tcc gcc aaa gag gtg ctg aac gcc cgg       2884
Gly Asp Arg Ile Phe Phe Val Ser Ala Lys Glu Val Leu Asn Ala Arg           
        300                 305                 310                       

att cag aaa gcc cag gga atg cct gaa ggc gga ggt gca ctg gcc gag       2932
Ile Gln Lys Ala Gln Gly Met Pro Glu Gly Gly Gly Ala Leu Ala Glu           
    315                 320                 325                           

gga ttt caa gtg cgg atg ttc gag ttc cag aac ttc gag cgg aga ttc       2980
Gly Phe Gln Val Arg Met Phe Glu Phe Gln Asn Phe Glu Arg Arg Phe           
330                 335                 340                 345           

gag gag tgc atc agc cag agc gcc gtc aag acc aag ttc gag cag cat       3028
Glu Glu Cys Ile Ser Gln Ser Ala Val Lys Thr Lys Phe Glu Gln His           
                350                 355                 360               

acc gtg cgg gcc aag cag att gcc gaa gcc gtc aga ctg atc atg gac       3076
Thr Val Arg Ala Lys Gln Ile Ala Glu Ala Val Arg Leu Ile Met Asp           
            365                 370                 375                   

agc ctg cat atg gcc gcc aga gag cag cag gtc tac tgc gag gaa atg       3124
Ser Leu His Met Ala Ala Arg Glu Gln Gln Val Tyr Cys Glu Glu Met           
        380                 385                 390                       

cgg gaa gag aga cag gac cgg ctg aag ttc atc gac aag cag ctg gaa       3172
Arg Glu Glu Arg Gln Asp Arg Leu Lys Phe Ile Asp Lys Gln Leu Glu           
    395                 400                 405                           

ctg ctg gcc cag gac tac aag ctg cgg atc aag cag atc acc gaa gag       3220
Leu Leu Ala Gln Asp Tyr Lys Leu Arg Ile Lys Gln Ile Thr Glu Glu           
410                 415                 420                 425           

gtg gaa aga cag gtg tcc acc gct atg gcc gag gaa atc aga cgg ctg       3268
Val Glu Arg Gln Val Ser Thr Ala Met Ala Glu Glu Ile Arg Arg Leu           
                430                 435                 440               

agc gtg ctg gtc gac gac tac cag atg gac ttt cac ccc tct cca gtg       3316
Ser Val Leu Val Asp Asp Tyr Gln Met Asp Phe His Pro Ser Pro Val           
            445                 450                 455                   

gtg ctg aaa gtc tac aaa aac gag ctg cac cgg cac atc gag gaa ggc       3364
Val Leu Lys Val Tyr Lys Asn Glu Leu His Arg His Ile Glu Glu Gly           
        460                 465                 470                       

ctg ggc aga aac atg agc gac aga tgc agc acc gcc atc acc aat agc       3412
Leu Gly Arg Asn Met Ser Asp Arg Cys Ser Thr Ala Ile Thr Asn Ser           
    475                 480                 485                           

ctg cag acc atg cag cag gac atg atc gac ggc ctg aaa cct ctg ctg       3460
Leu Gln Thr Met Gln Gln Asp Met Ile Asp Gly Leu Lys Pro Leu Leu           
490                 495                 500                 505           

cct gtg tcc gtc aga tcc cag atc gat atg ctg gtg ccc cgg cag tgc       3508
Pro Val Ser Val Arg Ser Gln Ile Asp Met Leu Val Pro Arg Gln Cys           
                510                 515                 520               

ttt agc ctg aac tac gac ctg aac tgc gac aag ctg tgc gcc gat ttc       3556
Phe Ser Leu Asn Tyr Asp Leu Asn Cys Asp Lys Leu Cys Ala Asp Phe           
            525                 530                 535                   

caa gag gac atc gag ttt cac ttc agc ctc ggc tgg aca atg ctg gtc       3604
Gln Glu Asp Ile Glu Phe His Phe Ser Leu Gly Trp Thr Met Leu Val           
        540                 545                 550                       

aac aga ttt ctg ggc ccc aag aac agc aga cgg gcc ctg atg ggc tac       3652
Asn Arg Phe Leu Gly Pro Lys Asn Ser Arg Arg Ala Leu Met Gly Tyr           
    555                 560                 565                           

aac gat cag gtg cag agg ccc att cct ctg aca ccc gcc aat cct agc       3700
Asn Asp Gln Val Gln Arg Pro Ile Pro Leu Thr Pro Ala Asn Pro Ser           
570                 575                 580                 585           

atg cct cca ctg cct cag ggc agc ctg aca caa gag gaa ttc atg gtg       3748
Met Pro Pro Leu Pro Gln Gly Ser Leu Thr Gln Glu Glu Phe Met Val           
                590                 595                 600               

tct atg gtc acc ggc ctg gcc agc ctg acc agc aga aca tct atg ggc       3796
Ser Met Val Thr Gly Leu Ala Ser Leu Thr Ser Arg Thr Ser Met Gly           
            605                 610                 615                   

atc ctg gtc gtc ggc ggc gtt gtg tgg aaa gct gtt ggc tgg cgg ctg       3844
Ile Leu Val Val Gly Gly Val Val Trp Lys Ala Val Gly Trp Arg Leu           
        620                 625                 630                       

atc gcc ctg agc ttt ggc ctg tat ggc ctg ctg tac gtg tac gag aga       3892
Ile Ala Leu Ser Phe Gly Leu Tyr Gly Leu Leu Tyr Val Tyr Glu Arg           
    635                 640                 645                           

ctg acc tgg acc acc aag gcc aaa gag cgg gcc ttc aag cgg cag ttt       3940
Leu Thr Trp Thr Thr Lys Ala Lys Glu Arg Ala Phe Lys Arg Gln Phe           
650                 655                 660                 665           

gtg gaa cac gcc tcc gag aaa ctg cag ctg gtg atc agc tac acc ggc       3988
Val Glu His Ala Ser Glu Lys Leu Gln Leu Val Ile Ser Tyr Thr Gly           
                670                 675                 680               

agc aat tgc agc cac cag gtg cag caa gag ctg tcc gga aca ttc gcc       4036
Ser Asn Cys Ser His Gln Val Gln Gln Glu Leu Ser Gly Thr Phe Ala           
            685                 690                 695                   

cac ctg tgt cag cag gtc gac gtg acc aga gag aac ctg gaa caa gag       4084
His Leu Cys Gln Gln Val Asp Val Thr Arg Glu Asn Leu Glu Gln Glu           
        700                 705                 710                       

atc gcc gcc atg aat aag aaa atc gag gtg ctc gac tcc ctg cag agc       4132
Ile Ala Ala Met Asn Lys Lys Ile Glu Val Leu Asp Ser Leu Gln Ser           
    715                 720                 725                           

aag gcc aag ctg ctg aga aac aag gcc ggc tgg ctg gac agc gag ctg       4180
Lys Ala Lys Leu Leu Arg Asn Lys Ala Gly Trp Leu Asp Ser Glu Leu           
730                 735                 740                 745           

aat atg ttc acc cac cag tac ctg cag cct agc cgc taa taaagcggcc        4229
Asn Met Phe Thr His Gln Tyr Leu Gln Pro Ser Arg                           
                750                 755                                   

gcctaaggct cgaggatctt tttccctctg ccaaaaatta tggggacatc atgaagcccc     4289

ttgagcatct gacttctggc taataaagga aatttatttt cattgcaata gtgtgttgga     4349

attttttgtg tctctcactc ggataaggat cttcctagag catggctacg tagataagta     4409

gcatggcggg ttaatcatta actacaagga acccctagtg atggagttgg ccactccctc     4469

tctgcgcgct cgctcgctca ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt     4529

tgcccgggcg gcctcagtga gcgagcgagc gcgcag                               4565


<210>  80
<211>  757
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  80

Met Ser Leu Leu Phe Ser Arg Cys Asn Ser Ile Val Thr Val Lys Lys 
1               5                   10                  15      


Asn Lys Arg His Met Ala Glu Val Asn Ala Ser Pro Leu Lys His Phe 
            20                  25                  30          


Val Thr Ala Lys Lys Lys Ile Asn Gly Ile Phe Glu Gln Leu Gly Ala 
        35                  40                  45              


Tyr Ile Gln Glu Ser Ala Thr Phe Leu Glu Asp Thr Tyr Arg Asn Ala 
    50                  55                  60                  


Glu Leu Asp Pro Val Thr Thr Glu Glu Gln Val Leu Asp Val Lys Gly 
65                  70                  75                  80  


Tyr Leu Ser Lys Val Arg Gly Ile Ser Glu Val Leu Ala Arg Arg His 
                85                  90                  95      


Met Lys Val Ala Phe Phe Gly Arg Thr Ser Asn Gly Lys Ser Thr Val 
            100                 105                 110         


Ile Asn Ala Met Leu Trp Asp Lys Val Leu Pro Ser Gly Ile Gly His 
        115                 120                 125             


Thr Thr Asn Cys Phe Leu Arg Val Glu Gly Thr Asp Gly His Glu Ala 
    130                 135                 140                 


Phe Leu Leu Thr Glu Gly Ser Glu Glu Lys Arg Ser Ala Lys Thr Val 
145                 150                 155                 160 


Asn Gln Leu Ala His Ala Leu His Gln Asp Lys Gln Leu His Ala Gly 
                165                 170                 175     


Ser Leu Val Ser Val Met Trp Pro Asn Ser Lys Cys Pro Leu Leu Lys 
            180                 185                 190         


Asp Asp Leu Val Leu Met Asp Ser Pro Gly Ile Asp Val Thr Thr Glu 
        195                 200                 205             


Leu Asp Ser Trp Ile Asp Lys Phe Cys Leu Asp Ala Asp Val Phe Val 
    210                 215                 220                 


Leu Val Ala Asn Ser Glu Ser Thr Leu Met Gln Thr Glu Lys His Phe 
225                 230                 235                 240 


Phe His Lys Val Ser Glu Arg Leu Ser Arg Pro Asn Ile Phe Ile Leu 
                245                 250                 255     


Asn Asn Arg Trp Asp Ala Ser Ala Ser Glu Pro Glu Tyr Met Glu Glu 
            260                 265                 270         


Val Arg Arg Gln His Met Glu Arg Cys Thr Ser Phe Leu Val Asp Glu 
        275                 280                 285             


Leu Gly Val Val Asp Arg Ser Gln Ala Gly Asp Arg Ile Phe Phe Val 
    290                 295                 300                 


Ser Ala Lys Glu Val Leu Asn Ala Arg Ile Gln Lys Ala Gln Gly Met 
305                 310                 315                 320 


Pro Glu Gly Gly Gly Ala Leu Ala Glu Gly Phe Gln Val Arg Met Phe 
                325                 330                 335     


Glu Phe Gln Asn Phe Glu Arg Arg Phe Glu Glu Cys Ile Ser Gln Ser 
            340                 345                 350         


Ala Val Lys Thr Lys Phe Glu Gln His Thr Val Arg Ala Lys Gln Ile 
        355                 360                 365             


Ala Glu Ala Val Arg Leu Ile Met Asp Ser Leu His Met Ala Ala Arg 
    370                 375                 380                 


Glu Gln Gln Val Tyr Cys Glu Glu Met Arg Glu Glu Arg Gln Asp Arg 
385                 390                 395                 400 


Leu Lys Phe Ile Asp Lys Gln Leu Glu Leu Leu Ala Gln Asp Tyr Lys 
                405                 410                 415     


Leu Arg Ile Lys Gln Ile Thr Glu Glu Val Glu Arg Gln Val Ser Thr 
            420                 425                 430         


Ala Met Ala Glu Glu Ile Arg Arg Leu Ser Val Leu Val Asp Asp Tyr 
        435                 440                 445             


Gln Met Asp Phe His Pro Ser Pro Val Val Leu Lys Val Tyr Lys Asn 
    450                 455                 460                 


Glu Leu His Arg His Ile Glu Glu Gly Leu Gly Arg Asn Met Ser Asp 
465                 470                 475                 480 


Arg Cys Ser Thr Ala Ile Thr Asn Ser Leu Gln Thr Met Gln Gln Asp 
                485                 490                 495     


Met Ile Asp Gly Leu Lys Pro Leu Leu Pro Val Ser Val Arg Ser Gln 
            500                 505                 510         


Ile Asp Met Leu Val Pro Arg Gln Cys Phe Ser Leu Asn Tyr Asp Leu 
        515                 520                 525             


Asn Cys Asp Lys Leu Cys Ala Asp Phe Gln Glu Asp Ile Glu Phe His 
    530                 535                 540                 


Phe Ser Leu Gly Trp Thr Met Leu Val Asn Arg Phe Leu Gly Pro Lys 
545                 550                 555                 560 


Asn Ser Arg Arg Ala Leu Met Gly Tyr Asn Asp Gln Val Gln Arg Pro 
                565                 570                 575     


Ile Pro Leu Thr Pro Ala Asn Pro Ser Met Pro Pro Leu Pro Gln Gly 
            580                 585                 590         


Ser Leu Thr Gln Glu Glu Phe Met Val Ser Met Val Thr Gly Leu Ala 
        595                 600                 605             


Ser Leu Thr Ser Arg Thr Ser Met Gly Ile Leu Val Val Gly Gly Val 
    610                 615                 620                 


Val Trp Lys Ala Val Gly Trp Arg Leu Ile Ala Leu Ser Phe Gly Leu 
625                 630                 635                 640 


Tyr Gly Leu Leu Tyr Val Tyr Glu Arg Leu Thr Trp Thr Thr Lys Ala 
                645                 650                 655     


Lys Glu Arg Ala Phe Lys Arg Gln Phe Val Glu His Ala Ser Glu Lys 
            660                 665                 670         


Leu Gln Leu Val Ile Ser Tyr Thr Gly Ser Asn Cys Ser His Gln Val 
        675                 680                 685             


Gln Gln Glu Leu Ser Gly Thr Phe Ala His Leu Cys Gln Gln Val Asp 
    690                 695                 700                 


Val Thr Arg Glu Asn Leu Glu Gln Glu Ile Ala Ala Met Asn Lys Lys 
705                 710                 715                 720 


Ile Glu Val Leu Asp Ser Leu Gln Ser Lys Ala Lys Leu Leu Arg Asn 
                725                 730                 735     


Lys Ala Gly Trp Leu Asp Ser Glu Leu Asn Met Phe Thr His Gln Tyr 
            740                 745                 750         


Leu Gln Pro Ser Arg 
        755         


<210>  81
<211>  2211
<212>  DNA
<213>  adeno-associated virus hu68


<220>
<221>  CDS
<222>  (1)..(2211)
<223>  AAVhu68

<400>  81
atg gct gcc gat ggt tat ctt cca gat tgg ctc gag gac aac ctc agt         48
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser           
1               5                   10                  15                

gaa ggc att cgc gag tgg tgg gct ttg aaa cct gga gcc cct caa ccc         96
Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro           
            20                  25                  30                    

aag gca aat caa caa cat caa gac aac gct cgg ggt ctt gtg ctt ccg        144
Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro           
        35                  40                  45                        

ggt tac aaa tac ctt gga ccc ggc aac gga ctc gac aag ggg gag ccg        192
Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro           
    50                  55                  60                            

gtc aac gaa gca gac gcg gcg gcc ctc gag cac gac aag gcc tac gac        240
Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp           
65                  70                  75                  80            

cag cag ctc aag gcc gga gac aac ccg tac ctc aag tac aac cac gcc        288
Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala           
                85                  90                  95                

gac gcc gag ttc cag gag cgg ctc aaa gaa gat acg tct ttt ggg ggc        336
Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly           
            100                 105                 110                   

aac ctc ggg cga gca gtc ttc cag gcc aaa aag agg ctt ctt gaa cct        384
Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro           
        115                 120                 125                       

ctt ggt ctg gtt gag gaa gcg gct aag acg gct cct gga aag aag agg        432
Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg           
    130                 135                 140                           

cct gta gag cag tct cct cag gaa ccg gac tcc tcc gtg ggt att ggc        480
Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Val Gly Ile Gly           
145                 150                 155                 160           

aaa tcg ggt gca cag ccc gct aaa aag aga ctc aat ttc ggt cag act        528
Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr           
                165                 170                 175               

ggc gac aca gag tca gtc ccc gac cct caa cca atc gga gaa cct ccc        576
Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro           
            180                 185                 190                   

gca gcc ccc tca ggt gtg gga tct ctt aca atg gct tca ggt ggt ggc        624
Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly           
        195                 200                 205                       

gca cca gtg gca gac aat aac gaa ggt gcc gat gga gtg ggt agt tcc        672
Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser           
    210                 215                 220                           

tcg gga aat tgg cat tgc gat tcc caa tgg ctg ggg gac aga gtc atc        720
Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile           
225                 230                 235                 240           

acc acc agc acc cga acc tgg gcc ctg ccc acc tac aac aat cac ctc        768
Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu           
                245                 250                 255               

tac aag caa atc tcc aac agc aca tct gga gga tct tca aat gac aac        816
Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn           
            260                 265                 270                   

gcc tac ttc ggc tac agc acc ccc tgg ggg tat ttt gac ttc aac aga        864
Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg           
        275                 280                 285                       

ttc cac tgc cac ttc tca cca cgt gac tgg caa aga ctc atc aac aac        912
Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn           
    290                 295                 300                           

aac tgg gga ttc cgg cct aag cga ctc aac ttc aag ctc ttc aac att        960
Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile           
305                 310                 315                 320           

cag gtc aaa gag gtt acg gac aac aat gga gtc aag acc atc gct aat       1008
Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn           
                325                 330                 335               

aac ctt acc agc acg gtc cag gtc ttc acg gac tca gac tat cag ctc       1056
Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu           
            340                 345                 350                   

ccg tac gtg ctc ggg tcg gct cac gag ggc tgc ctc ccg ccg ttc cca       1104
Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro           
        355                 360                 365                       

gcg gac gtt ttc atg att cct cag tac ggg tat cta acg ctt aat gat       1152
Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp           
    370                 375                 380                           

gga agc caa gcc gtg ggt cgt tcg tcc ttt tac tgc ctg gaa tat ttc       1200
Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe           
385                 390                 395                 400           

ccg tcg caa atg cta aga acg ggt aac aac ttc cag ttc agc tac gag       1248
Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu           
                405                 410                 415               

ttt gag aac gta cct ttc cat agc agc tat gct cac agc caa agc ctg       1296
Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu           
            420                 425                 430                   

gac cga ctc atg aat cca ctc atc gac caa tac ttg tac tat ctc tca       1344
Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser           
        435                 440                 445                       

aag act att aac ggt tct gga cag aat caa caa acg cta aaa ttc agt       1392
Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser           
    450                 455                 460                           

gtg gcc gga ccc agc aac atg gct gtc cag gga aga aac tac ata cct       1440
Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro           
465                 470                 475                 480           

gga ccc agc tac cga caa caa cgt gtc tca acc act gtg act caa aac       1488
Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn           
                485                 490                 495               

aac aac agc gaa ttt gct tgg cct gga gct tct tct tgg gct ctc aat       1536
Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn           
            500                 505                 510                   

gga cgt aat agc ttg atg aat cct gga cct gct atg gcc agc cac aaa       1584
Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys           
        515                 520                 525                       

gaa gga gag gac cgt ttc ttt cct ttg tct gga tct tta att ttt ggc       1632
Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly           
    530                 535                 540                           

aaa caa gga act gga aga gac aac gtg gat gcg gac aaa gtc atg ata       1680
Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile           
545                 550                 555                 560           

acc aac gaa gaa gaa att aaa act acc aac cca gta gca acg gag tcc       1728
Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser           
                565                 570                 575               

tat gga caa gtg gcc aca aac cac cag agt gcc caa gca cag gcg cag       1776
Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Ala Gln Ala Gln           
            580                 585                 590                   

acc ggc tgg gtt caa aac caa gga ata ctt ccg ggt atg gtt tgg cag       1824
Thr Gly Trp Val Gln Asn Gln Gly Ile Leu Pro Gly Met Val Trp Gln           
        595                 600                 605                       

gac aga gat gtg tac ctg caa gga ccc att tgg gcc aaa att cct cac       1872
Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His           
    610                 615                 620                           

acg gac ggc aac ttt cac cct tct ccg ctg atg gga ggg ttt gga atg       1920
Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Met           
625                 630                 635                 640           

aag cac ccg cct cct cag atc ctc atc aaa aac aca cct gta cct gcg       1968
Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala           
                645                 650                 655               

gat cct cca acg gct ttc aac aag gac aag ctg aac tct ttc atc acc       2016
Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys Leu Asn Ser Phe Ile Thr           
            660                 665                 670                   

cag tat tct act ggc caa gtc agc gtg gag att gag tgg gag ctg cag       2064
Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln           
        675                 680                 685                       

aag gaa aac agc aag cgc tgg aac ccg gag atc cag tac act tcc aac       2112
Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn           
    690                 695                 700                           

tat tac aag tct aat aat gtt gaa ttt gct gtt aat act gaa ggt gtt       2160
Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala Val Asn Thr Glu Gly Val           
705                 710                 715                 720           

tat tct gaa ccc cgc ccc att ggc acc aga tac ctg act cgt aat ctg       2208
Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu           
                725                 730                 735               

taa                                                                   2211


<210>  82
<211>  736
<212>  PRT
<213>  adeno-associated virus hu68

<400>  82

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 
        115                 120                 125             


Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Val Gly Ile Gly 
145                 150                 155                 160 


Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 
            180                 185                 190         


Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 
            260                 265                 270         


Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 
        275                 280                 285             


Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 
    290                 295                 300                 


Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 
305                 310                 315                 320 


Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 
                325                 330                 335     


Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu 
            340                 345                 350         


Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 
        355                 360                 365             


Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 
    370                 375                 380                 


Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 
385                 390                 395                 400 


Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 
                405                 410                 415     


Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 
            420                 425                 430         


Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 
        435                 440                 445             


Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 
    450                 455                 460                 


Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 
465                 470                 475                 480 


Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 
                485                 490                 495     


Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn 
            500                 505                 510         


Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 
        515                 520                 525             


Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 
    530                 535                 540                 


Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 
545                 550                 555                 560 


Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 
                565                 570                 575     


Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Ala Gln Ala Gln 
            580                 585                 590         


Thr Gly Trp Val Gln Asn Gln Gly Ile Leu Pro Gly Met Val Trp Gln 
        595                 600                 605             


Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 
    610                 615                 620                 


Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Met 
625                 630                 635                 640 


Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 
                645                 650                 655     


Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys Leu Asn Ser Phe Ile Thr 
            660                 665                 670         


Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 
        675                 680                 685             


Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 
    690                 695                 700                 


Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala Val Asn Thr Glu Gly Val 
705                 710                 715                 720 


Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 
                725                 730                 735     


<210>  83
<211>  2211
<212>  DNA
<213>  adeno-associated virus hu68

<400>  83
atggctgccg atggttatct tccagattgg ctcgaggaca acctcagtga aggcattcgc       60

gagtggtggg ctttgaaacc tggagcccct caacccaagg caaatcaaca acatcaagac      120

aacgctcggg gtcttgtgct tccgggttac aaataccttg gacccggcaa cggactcgac      180

aagggggagc cggtcaacga agcagacgcg gcggccctcg agcacgacaa ggcctacgac      240

cagcagctca aggccggaga caacccgtac ctcaagtaca accacgccga cgccgagttc      300

caggagcggc tcaaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag      360

gccaaaaaga ggcttcttga acctcttggt ctggttgagg aagcggctaa gacggctcct      420

ggaaagaaga ggcctgtaga gcagtctcct caggaaccgg actcctccgt gggtattggc      480

aaatcgggtg cacagcccgc taaaaagaga ctcaatttcg gtcagactgg cgacacagag      540

tcagtccccg accctcaacc aatcggagaa cctcccgcag ccccctcagg tgtgggatct      600

cttacaatgg cttcaggtgg tggcgcacca gtggcagaca ataacgaagg tgccgatgga      660

gtgggtagtt cctcgggaaa ttggcattgc gattcccaat ggctggggga cagagtcatc      720

accaccagca cccgaacctg ggccctgccc acctacaaca atcacctcta caagcaaatc      780

tccaacagca catctggagg atcttcaaat gacaacgcct acttcggcta cagcaccccc      840

tgggggtatt ttgacttcaa cagattccac tgccacttct caccacgtga ctggcaaaga      900

ctcatcaaca acaactgggg attccggcct aagcgactca acttcaagct cttcaacatt      960

caggtcaaag aggttacgga caacaatgga gtcaagacca tcgctaataa ccttaccagc     1020

acggtccagg tcttcacgga ctcagactat cagctcccgt acgtgctcgg gtcggctcac     1080

gagggctgcc tcccgccgtt cccagcggac gttttcatga ttcctcagta tggatacctc     1140

accctgaacg acggcagtca ggcggtgggc cgctcatcct tctactgcct ggagtacttc     1200

ccttcgcaga tgctgaggac tggcaacaac ttccagttca gctacgagtt cgagaacgtc     1260

cctttccaca gcagctacgc ccacagccag agtttggacc gcttgatgaa ccctctgatc     1320

gaccagtacc tgtactacct gtcaaagacg atcaacggtt ctggccagaa ccagcagacg     1380

ctgaagttca gcgtggccgg gcctagcaac atggccgtcc agggcagaaa ctacatccct     1440

gggcccagct accggcagca gagagtctca accactgtga ctcagaacaa caacagtgag     1500

ttcgcctggc ctggcgccag ctcttgggcc ctcaacggcc gcaactcgct gatgaaccca     1560

ggcccagcca tggccagtca caaggagggc gaggaccgtt tcttcccttt gtctggctct     1620

ctgatcttcg gcaagcaggg gaccggcaga gacaacgtgg acgcggacaa ggtcatgatc     1680

acgaacgagg aggagatcaa gaccaccaac cctgtggcaa ccgagtccta cggccaggtg     1740

gcaaccaacc accagagcgc ccaggcacag gcgcagactg gctgggtcca gaaccagggg     1800

atcctgcctg gcatggtgtg gcaggaccgt gacgtgtacc tgcagggccc tatctgggca     1860

aagatccctc acacggacgg caacttccac ccttctcctc tgatgggcgg cttcggcatg     1920

aagcacccgc ctcctcagat cctcatcaag aacactccgg tcccggcaga ccctccgacg     1980

gccttcaaca aggacaagct gaactcattc atcactcagt actccactgg ccaggtcagc     2040

gtggagatcg agtgggagct gcagaaggag aacagcaagc gttggaaccc agagatccag     2100

tacacttcca actactacaa gtctaacaac gtggagttcg ccgtcaacac tgagggtgtg     2160

tacagtgagc ctcgccctat cggcacccgg tacctcaccc gaaacttgtg a              2211


<210>  84
<211>  2229
<212>  DNA
<213>  adeno-associated virus PHP.eB


<220>
<221>  CDS
<222>  (1)..(2229)
<223>  AAV-PHP.eB

<400>  84
atg gct gcc gat ggt tat ctt cca gat tgg ctc gag gac aac ctt agt         48
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser           
1               5                   10                  15                

gaa gga att cgc gag tgg tgg gct ttg aaa cct gga gcc cct caa ccc         96
Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro           
            20                  25                  30                    

aag gca aat caa caa cat caa gac aac gct aga ggt ctt gtg ctt ccg        144
Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro           
        35                  40                  45                        

ggt tac aaa tac ctt gga ccc ggc aac gga ctc gac aag ggg gag ccg        192
Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro           
    50                  55                  60                            

gtc aac gca gca gac gcg gcg gcc ctc gag cac gac aaa gcc tac gac        240
Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp           
65                  70                  75                  80            

cag cag ctc aag gcc gga gac aac ccg tac ctc aag tac aac cac gcc        288
Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala           
                85                  90                  95                

gac gcc gag ttc cag gag cgg ctc aaa gaa gat acg tct ttt ggg ggc        336
Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly           
            100                 105                 110                   

aac ctc ggg cga gca gtc ttc cag gcc aaa aag agg ctt ctt gaa cct        384
Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro           
        115                 120                 125                       

ctt ggt ctg gtt gag gaa gcg gct aag acg gct cct gga aag aag agg        432
Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg           
    130                 135                 140                           

cct gta gag cag tct cct cag gaa ccg gac tcc tcc gcg ggt att ggc        480
Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly           
145                 150                 155                 160           

aaa tcg ggt gca cag ccc gct aaa aag aga ctc aat ttc ggt cag act        528
Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr           
                165                 170                 175               

ggc gac aca gag tca gtc cca gac cct caa cca atc gga gaa cct ccc        576
Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro           
            180                 185                 190                   

gca gcc ccc tca ggt gtg gga tct ctt aca atg gct tca ggt ggt ggc        624
Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly           
        195                 200                 205                       

gca cca gtg gca gac aat aac gaa ggt gcc gat gga gtg ggt agt tcc        672
Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser           
    210                 215                 220                           

tcg gga aat tgg cat tgc gat tcc caa tgg ctg ggg gac aga gtc atc        720
Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile           
225                 230                 235                 240           

acc acc agc acc cga acc tgg gcc ctg ccc acc tac aac aat cac ctc        768
Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu           
                245                 250                 255               

tac aag caa atc tcc aac agc aca tct gga gga tct tca aat gac aac        816
Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn           
            260                 265                 270                   

gcc tac ttc ggc tac agc acc ccc tgg ggg tat ttt gac ttc aac aga        864
Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg           
        275                 280                 285                       

ttc cac tgc cac ttc tca cca cgt gac tgg cag cga ctc atc aac aac        912
Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn           
    290                 295                 300                           

aac tgg gga ttc cgg cct aag cga ctc aac ttc aag ctc ttt aac att        960
Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile           
305                 310                 315                 320           

cag gtc aaa gag gtt acg gac aac aat gga gtc aag acc atc gcc aat       1008
Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn           
                325                 330                 335               

aac ctt acc agc acg gtc cag gtc ttc acg gac tca gac tat cag ctc       1056
Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu           
            340                 345                 350                   

ccg tac gtg ctc ggg tcg gct cac gag ggc tgc ctc ccg ccg ttc cca       1104
Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro           
        355                 360                 365                       

gcg gac gtt ttc atg att cct cag tac ggg tat ctg acg ctt aat gat       1152
Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp           
    370                 375                 380                           

gga agc cag gcc gtg ggt cgt tcg tcc ttt tac tgc ctg gaa tat ttc       1200
Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe           
385                 390                 395                 400           

ccg tcg caa atg cta aga acg ggt aac aac ttc cag ttc agc tac gag       1248
Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu           
                405                 410                 415               

ttt gag aac gta cct ttc cat agc agc tac gct cac agc caa agc ctg       1296
Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu           
            420                 425                 430                   

gac cga cta atg aat cca ctc atc gac caa tac ttg tac tat ctc tct       1344
Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser           
        435                 440                 445                       

aga act att aac ggt tct gga cag aat caa caa acg cta aaa ttc agt       1392
Arg Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser           
    450                 455                 460                           

gtg gcc gga ccc agc aac atg gct gtc cag gga aga aac tac ata cct       1440
Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro           
465                 470                 475                 480           

gga ccc agc tac cga caa caa cgt gtc tca acc act gtg act caa aac       1488
Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn           
                485                 490                 495               

aac aac agc gaa ttt gct tgg cct gga gct tct tct tgg gct ctc aat       1536
Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn           
            500                 505                 510                   

gga cgt aat agc ttg atg aat cct gga cct gct atg gcc tct cac aaa       1584
Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys           
        515                 520                 525                       

gaa gga gag gac cgt ttc ttt cct ttg tct gga tct tta att ttt ggc       1632
Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly           
    530                 535                 540                           

aaa caa ggt act ggc aga gac aac gtg gat gcg gac aaa gtc atg ata       1680
Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile           
545                 550                 555                 560           

acc aac gaa gaa gaa att aaa act act aac ccg gta gca acg gag tcc       1728
Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser           
                565                 570                 575               

tat gga caa gtg gcc aca aac cac cag agt gat ggg act ttg gcg gtg       1776
Tyr Gly Gln Val Ala Thr Asn His Gln Ser Asp Gly Thr Leu Ala Val           
            580                 585                 590                   

cct ttt aag gca cag gcg cag acc ggt tgg gtt caa aac caa gga ata       1824
Pro Phe Lys Ala Gln Ala Gln Thr Gly Trp Val Gln Asn Gln Gly Ile           
        595                 600                 605                       

ctt ccg ggt atg gtt tgg cag gac aga gat gtg tac ctg caa gga ccc       1872
Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro           
    610                 615                 620                           

att tgg gcc aaa att cct cac acg gac ggc aac ttt cac cct tct ccg       1920
Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro           
625                 630                 635                 640           

ctg atg gga ggg ttt gga atg aag cac ccg cct cct cag atc ctc atc       1968
Leu Met Gly Gly Phe Gly Met Lys His Pro Pro Pro Gln Ile Leu Ile           
                645                 650                 655               

aaa aac aca cct gta cct gcg gat cct cca acg gcc ttc aac aag gac       2016
Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Ala Phe Asn Lys Asp           
            660                 665                 670                   

aag ctg aac tct ttc atc acc cag tat tct act ggt caa gtc agc gtg       2064
Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val           
        675                 680                 685                       

gag atc gag tgg gag ctg cag aag gaa aac agc aag cgc tgg aac ccg       2112
Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro           
    690                 695                 700                           

gag atc cag tac act tcc aac tat tac aag tct aat aat gtt gaa ttt       2160
Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Asn Asn Val Glu Phe           
705                 710                 715                 720           

gct gtt aat act gaa ggt gta tat agt gaa ccc cgc ccc att ggc acc       2208
Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr           
                725                 730                 735               

aga tac ctg act cgt aat ctg                                           2229
Arg Tyr Leu Thr Arg Asn Leu                                               
            740                                                           


<210>  85
<211>  743
<212>  PRT
<213>  adeno-associated virus PHP.eB

<400>  85

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 
        115                 120                 125             


Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly 
145                 150                 155                 160 


Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 
            180                 185                 190         


Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 
            260                 265                 270         


Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 
        275                 280                 285             


Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 
    290                 295                 300                 


Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 
305                 310                 315                 320 


Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 
                325                 330                 335     


Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu 
            340                 345                 350         


Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 
        355                 360                 365             


Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 
    370                 375                 380                 


Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 
385                 390                 395                 400 


Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 
                405                 410                 415     


Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 
            420                 425                 430         


Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 
        435                 440                 445             


Arg Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 
    450                 455                 460                 


Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 
465                 470                 475                 480 


Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 
                485                 490                 495     


Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn 
            500                 505                 510         


Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 
        515                 520                 525             


Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 
    530                 535                 540                 


Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 
545                 550                 555                 560 


Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 
                565                 570                 575     


Tyr Gly Gln Val Ala Thr Asn His Gln Ser Asp Gly Thr Leu Ala Val 
            580                 585                 590         


Pro Phe Lys Ala Gln Ala Gln Thr Gly Trp Val Gln Asn Gln Gly Ile 
        595                 600                 605             


Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro 
    610                 615                 620                 


Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro 
625                 630                 635                 640 


Leu Met Gly Gly Phe Gly Met Lys His Pro Pro Pro Gln Ile Leu Ile 
                645                 650                 655     


Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Ala Phe Asn Lys Asp 
            660                 665                 670         


Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val 
        675                 680                 685             


Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro 
    690                 695                 700                 


Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Asn Asn Val Glu Phe 
705                 710                 715                 720 


Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr 
                725                 730                 735     


Arg Tyr Leu Thr Arg Asn Leu 
            740             


<210>  86
<211>  841
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CB7 Promoter with CMV enhancer

<400>  86
ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac tttccattga       60

cgtcaatggg tggagtattt acggtaaact gcccacttgg cagtacatca agtgtatcat      120

atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg gcattatgcc      180

cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt agtcatcgct      240

attaccatgg tcgaggtgag ccccacgttc tgcttcactc tccccatctc ccccccctcc      300

ccacccccaa ttttgtattt atttattttt taattatttt gtgcagcgat gggggcgggg      360

gggggggggg ggcgcgcgcc aggcggggcg gggcggggcg aggggcgggg cggggcgagg      420

cggagaggtg cggcggcagc caatcagagc ggcgcgctcc gaaagtttcc ttttatggcg      480

aggcggcggc ggcggcggcc ctataaaaag cgaagcgcgc ggcgggcggg agtcgctgcg      540

cgctgccttc gccccgtgcc ccgctccgcc gccgcctcgc gccgcccgcc ccggctctga      600

ctgaccgcgt tactcccaca ggtgagcggg cgggacggcc cttctcctcc gggctgtaat      660

tagcgcttgg tttaatgacg gcttgtttct tttctgtggc tgcgtgaaag ccttgagggg      720

ctccgggagg gccctttgtg cggggggagc ggctcggggc tgtccgcggg gggacggctg      780

ccttcggggg ggacggggca gggcggggtt cggcttctgg cgtgtgaccg gcggctctag      840

a                                                                      841


<210>  87
<211>  841
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CAG promoter

<400>  87
ccattgacgt caataatgac gtatgttccc atagtaacgc caatagggac tttccattga       60

cgtcaatggg tggagtattt acggtaaact gcccacttgg cagtacatca agtgtatcat      120

atgccaagta cgccccctat tgacgtcaat gacggtaaat ggcccgcctg gcattatgcc      180

cagtacatga ccttatggga ctttcctact tggcagtaca tctacgtatt agtcatcgct      240

attaccatgg tcgaggtgag ccccacgttc tgcttcactc tccccatctc ccccccctcc      300

ccacccccaa ttttgtattt atttattttt taattatttt gtgcagcgat gggggcgggg      360

gggggggggg ggcgcgcgcc aggcggggcg gggcggggcg aggggcgggg cggggcgagg      420

cggagaggtg cggcggcagc caatcagagc ggcgcgctcc gaaagtttcc ttttatggcg      480

aggcggcggc ggcggcggcc ctataaaaag cgaagcgcgc ggcgggcggg agtcgctgcg      540

cgctgccttc gccccgtgcc ccgctccgcc gccgcctcgc gccgcccgcc ccggctctga      600

ctgaccgcgt tactcccaca ggtgagcggg cgggacggcc cttctcctcc gggctgtaat      660

tagcgcttgg tttaatgacg gcttgtttct tttctgtggc tgcgtgaaag ccttgagggg      720

ctccgggagg gccctttgtg cggggggagc ggctcggggc tgtccgcggg gggacggctg      780

ccttcggggg ggacggggca gggcggggtt cggcttctgg cgtgtgaccg gcggctctag      840

a                                                                      841


<210>  88
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rabbit beta-globin

<400>  88
gatctttttc cctctgccaa aaattatggg gacatcatga agccccttga gcatctgact       60

tctggctaat aaaggaaatt tattttcatt gcaatagtgt gttggaattt tttgtgtctc      120

tcactcg                                                                127


<210>  89
<211>  59
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  miR1538

<400>  89
ttgacgtcca gaacctgttc tgttttggcc actgactgac agaacaggct ggacgtcaa        59


<210>  90
<211>  82
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  linker

<400>  90
taaagcggcc gcaagcttgc acccgtacct ttgggagcgc gcgccctcgt cgtgtcgtga       60

cgtcacccgt tctgttggat cc                                                82


