                         SEQUENCE LISTING

<110>  Wang, Zhengne
 
<120>  TARGETED GENE MODIFICATION USING HYBRID RECOMBINANT 
       ADENO-ASSOCIATED VIRUS

<130>  CWR-020982US ORD

<150>  61/579,744
<151>  2011-12-23

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  738
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Capsid protein of adeno-associated virus serotype 8

<400>  1

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 Lys Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe 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 Gln Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 
        115                 120                 125             


Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile 
145                 150                 155                 160 


Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln 
                165                 170                 175     


Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro 
            180                 185                 190         


Pro Ala Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ala Gly Gly 
        195                 200                 205             


Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 
    210                 215                 220                 


Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 
225                 230                 235                 240 


Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 
                245                 250                 255     


Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ala Thr Asn Asp 
            260                 265                 270         


Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 
        275                 280                 285             


Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn 
    290                 295                 300                 


Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn 
305                 310                 315                 320 


Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala 
                325                 330                 335     


Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 
            340                 345                 350         


Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe 
        355                 360                 365             


Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 
    370                 375                 380                 


Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 
385                 390                 395                 400 


Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr 
                405                 410                 415     


Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 
            420                 425                 430         


Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu 
        435                 440                 445             


Ser Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly 
    450                 455                 460                 


Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp 
465                 470                 475                 480 


Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly 
                485                 490                 495     


Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His 
            500                 505                 510         


Leu Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr 
        515                 520                 525             


His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile 
    530                 535                 540                 


Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val 
545                 550                 555                 560 


Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 
                565                 570                 575     


Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala 
            580                 585                 590         


Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val 
        595                 600                 605             


Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile 
    610                 615                 620                 


Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe 
625                 630                 635                 640 


Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val 
                645                 650                 655     


Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe 
            660                 665                 670         


Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu 
        675                 680                 685             


Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr 
    690                 695                 700                 


Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu 
705                 710                 715                 720 


Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 
                725                 730                 735     


Asn Leu 
        


<210>  2
<211>  737
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic capsid protein

<400>  2

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 
            20                  25                  30          


Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe 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  


Arg Gln Leu Asp Ser 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 His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly 
145                 150                 155                 160 


Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Ala Asp 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 Ala Gly Gly Gly 
        195                 200                 205             


Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met 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 Ser Phe Lys Leu Phe Asn Ile 
305                 310                 315                 320 


Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala Asn 
                325                 330                 335     


Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu 
            340                 345                 350         


Pro Tyr Val Leu Gly Ser Ala His Gln 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 Asn 
    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 Lys Thr Gly Asn Asn Phe Gln Phe Thr Tyr Thr 
                405                 410                 415     


Phe Glu Asp 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 Gln Thr Thr Gly Gly Thr Thr Asn Thr Gln Thr Leu Gly Phe 
    450                 455                 460                 


Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu 
465                 470                 475                 480 


Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp 
                485                 490                 495     


Asn Asn Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu 
            500                 505                 510         


Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His 
        515                 520                 525             


Lys Asp Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe 
    530                 535                 540                 


Gly Lys Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met 
545                 550                 555                 560 


Ile Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu 
                565                 570                 575     


Gln Tyr Gly Ser Val Ser Thr Asn Leu Gln Arg Gly Asn Arg Gln Ala 
            580                 585                 590         


Ala Thr Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp 
        595                 600                 605             


Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro 
    610                 615                 620                 


His Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly 
625                 630                 635                 640 


Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro 
                645                 650                 655     


Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile 
            660                 665                 670         


Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu 
        675                 680                 685             


Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser 
    690                 695                 700                 


Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly 
705                 710                 715                 720 


Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn 
                725                 730                 735     


Leu 
    


<210>  3
<211>  2215
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic capsid protein encoding sequence

<400>  3
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga       60

cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac      120

gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac      180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa agcctacgac      240

cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgccgagttc      300

caggagcggc tcaaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag      360

gccaaaaaga ggcttcttga acctcttggt ctggttgagg aagcggctaa gacggctcct      420

ggaaagaaga ggcctgtaga gcactctcct gtggagccag actcctcctc gggaaccgga      480

aaggcgggcc agcagcctgc aagaaaaaga ttgaattttg gtcagactgg agacgcagac      540

tcagtcccag accctcaacc aatcggagaa cctcccgcag ccccctcagg tgtgggatct      600

cttacaatgg ctgcaggcgg tggcgcacca atggcagaca ataacgaggg cgccgacgga      660

gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc      720

accaccagca cccgaacctg ggccctgccc acctacaaca accacctcta caagcaaatc      780

tccaacagca catctggagg atcttcaaat gacaacgcct acttcggcta cagcaccccc      840

tgggggtatt ttgactttaa cagattccac tgccactttt caccacgtga ctggcagcga      900

ctcatcaaca acaactgggg attccggccc aagagactca gcttcaagct cttcaacatc      960

caggtcaagg aggtcacgca gaatgaaggc accaagacca tcgccaataa cctcaccagc     1020

accatccagg tgtttacgga ctcggagtac cagctgccgt acgttctcgg ctctgcccac     1080

cagggctgcc tgcctccgtt cccggcggac gtgttcatga ttccccagta cggctaccta     1140

acactcaaca acggtagtca ggccgtggga cgctcctcct tctactgcct ggaatacttt     1200

ccttcgcaga tgctgagaac cggcaacaac ttccagttta cttacacctt cgaggacgtg     1260

cctttccaca gcagctacgc ccacagccag agcttggacc ggctgatgaa tcctctgatt     1320

gaccagtacc tgtactactt gtctcggact caaacaacag gaggcacgac aaatacgcag     1380

actctgggct tcagccaagg tgggcctaat acaatggcca atcaggcaaa gaactggctg     1440

ccaggaccct gttaccgcca gcagcgagta tcaaagacat ctgcggataa caacaacagt     1500

gaatactcgt ggactggagc taccaagtac cacctcaatg gcagagactc tctggtgaat     1560

ccgggcccgg ccatggcaag ccacaaggac gatgaagaaa agtttttttc ctcagagcgg     1620

ggttctcatc tttgggaagc aaggctcaga gaaaacaaat gtggacattg aaaaggtcat     1680

gattacagac gaagaggaaa tcaggacaac caatcccgtg gctacggagc agtatggttc     1740

tgtatctacc aacctccaga gaggcaacag acaagcagct accgcagatg tcaacacaca     1800

aggcgttctt ccaggcatgg tctggcagga cagagatgtg taccttcagg ggcccatctg     1860

ggcaaagatt ccacacacgg acggacattt tcacccctct cccctcatgg gtggattcgg     1920

acttaaacac cctccgcctc agatcctgat caagaacacg cctgtacctg cggatcctcc     1980

gaccaccttc aaccagtcaa agctgaactc tttcatcacc cagtattcta ctggccaagt     2040

cagcgtggag atcgagtggg agctgcagaa ggaaaacagc aagcgctgga accccgagat     2100

ccagtacacc tccaactact acaaatctac aagtgtggac tttgctgtta atacagaagg     2160

cgtgtactct gaaccccgcc ccattggcac ccgttacctc acccgtaatc tgtaa          2215


