                         SEQUENCE LISTING

<110>  Kiromic LLC
 
<120>  COMPOSITIONS AND METHODS FOR TREATING CARDIOVASCULAR DISEASES 
       USING SMAD3

<130>  5091-0002-CIP-PCT

<150>  US 14/508,642
<151>  2014-10-07

<150>  US 61/979,789
<151>  2014-04-15

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  2420
<212>  DNA
<213>  homo sapien

<400>  1
atgaggccca cctacattat gcagcgaaat ctactttcct ctgctgatta atatgttaat       60

ctcatttaaa agcatcctgt ctgggaaccc catgacccag tcaagaagac acagaaggcc      120

agcacggtgg ctcacggctt gtaatcccag cactgtggga ggctgaggca ggcggatcac      180

ttgaggacag gagttcaaga ccagcctggc caacatggtg aaaccctgtc tctactgaaa      240

atacaaaaca attagccggg aggggtggcg ggcacctgta atcccagcta ctcaggaggc      300

tgaggcagga gaattgcttg aacccaggag gcggaggttg cagtgagccg agatcatgcc      360

attgcaaccc accctgggta acaagggcga aactccatct caaaaacaaa caaacaaaca      420

aacaaacaaa caaaacacat gaaattcacc atcacaggag ttattgcttg gtgggtatag      480

agtttcagtt ggggaagatg aaaagttctg gagatggatg gtggtgatgg ctgcacaaca      540

atgtaaatgt acttaatgcc actgaacagt acgcctaaaa atggttgaaa tggtaaacac      600

tttatgttct ataatattca tggcatccaa aataactgag tcactgtaga aatgataatg      660

tgcccttttc agtgtgatat cgtttcagta ttttttaatt cttttttttt ttttttttaa      720

agggagtctc gctctgttgc ccaggctgga gtacagtggc acaatctcag ctcactgaaa      780

atgaaaagca ttttcatttt ccacctccca aatagctggg attataggct tgcaaccagg      840

cccagctaac ttttgtattt ttagtggtga cagggtttca acaggttggc caggctggtc      900

tcgaactcct gacctcagtg atccaccccc ccctcagctt cccaaagtgc tgagattaca      960

ggcatgagcc actgcacctg gccaactttt tcaatttgtt ctcaaatact ctgcacataa     1020

taaaaggaat ataggaaaca gggaggagga gggaaatgga atcctaatta ggctgtcaat     1080

attggtaatt tttcctaata gtttcctata tgttttattt atgtatttat ttttccattc     1140

ttcctttgtg tattcttttc tttgcacttt tttttcctgg agtaatttaa agtaaatgcc     1200

agatatcata tcattttgct tataaatact tccttcagaa gacatctcta atagatatat     1260

atctggttag gaggttgtca agggaaaata gaaaagtatt ctatcagtaa atacatatag     1320

acatacttat gggtctctca tgtaagcgtc tttgtgacat gagtcaatca tggattttac     1380

tgaaatacat tatttgatgg gtaattcaac tgtgctgaat attagtacta tactaataat     1440

tattatttat tggcttctta ttatgctcca agtacaaagc ttgtcatttt taaccagcgt     1500

gtcatttgaa ttcctatagc aacgtgacat ttttcacaaa cctagtgtaa aaaagcttat     1560

tatttttacc cagcatgtca tttgaattcc tataacaatg ttatcaggta gacattatcc     1620

ctaatttcca gacatgtcat ttgaattcct ataacaatgt tatcaggtag acattatccc     1680

taatttccag acaaagacat agattcaaag tattaagatt tcccaagatt gtagactaaa     1740

ggaaagtact gaaactagct ctttctgcat tcaaagtgct ctctgctgct acgttacact     1800

ggcactgcat gaactagtag ccccagataa attctaaaat cacccaggac acaccatcgc     1860

tggaaatggg agccatatgt gattcacccc aaaattctta gatccattgc cagataaaac     1920

agtgataatc aaaagagaat atatctgatt cataaaagac accatataga aacagtctgc     1980

taatgaaatt agcaaacaaa cattggaatc aaatattttg gcccataatt ctggcacatt     2040

ttttacaaat gtagtgtgac ttactctctt tgaatttcag tttctgtctc tgaagagtgg     2100

gtacaatatc tcctctgatg ctcatgaaaa atagttttcc ctttcataaa ttacttagcg     2160

aaatatcctg aaacaccttc agaatcacca ctttctccac ctgcaataca cataactcaa     2220

gaatttgcgt cagcgaactt cccaatatga agcaaagcct ctccttcctc ctaccaatga     2280

ttgagccatt cttctattag ataacagtag ctatttaaat acttctgcag aagctcacat     2340

atttttagtt tgttgaagtt cgtgactgct tcactctctc attcttagct tgaatttgga     2400

aatgactttt gatgacctaa                                                 2420


<210>  2
<211>  460
<212>  DNA
<213>  homo sapien

<400>  2
aaagaaggca tgcacagctc agcactgctc tgttgcctgg tcctcctgac tggggtgagg       60

gccagcccag gccagggcac ccagtctgag aacagctgca cccacttccc aggcaacctg      120

cctaacatgc ttcgagatct ccgagatgcc ttcagcagag tgaagacttt ctttcaaatg      180

aaggatcagc tggacaactt gttgttaaag gagtccttgc tggaggactt taagggttac      240

ctgggttgcc aagccttgtc tgagatgatc cagttttacc tggaggaggt gatgccccaa      300

gctgagaacc aagacccaga catcaaggcg catgtgaact ccctggggga gaacctgaag      360

accctcaggc tgaggctacg gcgctgtcat cgatttcttc cctgtgaaaa caagagcaag      420

gccgtggagc aggtgaagaa tgcctttaat aagctccaag                            460


<210>  3
<211>  2217
<212>  DNA
<213>  artificial sequence

<220>
<223>  AAV8 capsid coding (nucleotide) sequence with Tyr447 and Tyr 733 
       mutated to Phe residues

<400>  3
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc       60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac      120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac      180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac      240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt      300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag      360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct      420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc      480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca      540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga      600

cctaatacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggcgccgac      660

ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc      720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa      780

atctccaacg ggacatcggg aggagccacc aacgacaaca cctacttcgg ctacagcacc      840

ccctgggggt attttgactt taacagattc cactgccact tttcaccacg tgactggcag      900

cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac      960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc     1020

agcaccatcc aggtgtttac ggactcggag taccagctgc cgtacgttct cggctctgcc     1080

caccagggct gcctgcctcc gttcccggcg gacgtgttca tgattcccca gtacggctac     1140

ctaacactca acaacggtag tcaggccgtg ggacgctcct ccttctactg cctggaatac     1200

tttccttcgc agatgctgag aaccggcaac aacttccagt ttacttacac cttcgaggac     1260

gtgcctttcc acagcagcta cgcccacagc cagagcttgg accggctgat gaatcctctg     1320

attgaccagt acctgtactt cttgtctcgg actcaaacaa caggaggcac ggcaaatacg     1380

cagactctgg gcttcagcca aggtgggcct aatacaatgg ccaatcaggc aaagaactgg     1440

ctgccaggac cctgttaccg ccaacaacgc gtctcaacga caaccgggca aaacaacaat     1500

agcaactttg cctggactgc tgggaccaaa taccatctga atggaagaaa ttcattggct     1560

aatcctggca tcgctatggc aacacacaaa gacgacgagg agcgtttttt tcccagtaac     1620

gggatcctga tttttggcaa acaaaatgct gccagagaca atgcggatta cagcgatgtc     1680

atgctcacca gcgaggaaga aatcaaaacc actaaccctg tggctacaga ggaatacggt     1740

atcgtggcag ataacttgca gcagcaaaac acggctcctc aaattggaac tgtcaacagc     1800

cagggggcct tacccggtat ggtctggcag aaccgggacg tgtacctgca gggtcccatc     1860

tgggccaaga ttcctcacac ggacggcaac ttccacccgt ctccgctgat gggcggcttt     1920

ggcctgaaac atcctccgcc tcagatcctg atcaagaaca cgcctgtacc tgcggatcct     1980

ccgaccacct tcaaccagtc aaagctgaac tctttcatca cgcaatacag caccggacag     2040

gtcagcgtgg aaattgaatg ggagctgcag aaggaaaaca gcaagcgctg gaaccccgag     2100

atccagtaca cctccaacta ctacaaatct acaagtgtgg actttgctgt taatacagaa     2160

ggcgtgtact ctgaaccccg ccccattggc acccgtttcc tcacccgtaa tctgtaa        2217


<210>  4
<211>  738
<212>  PRT
<213>  artificial sequence

<220>
<223>  AAV8 capsid amino acid sequence with Tyr447 and Tyr 733 mutated 
       to Phe residues

<400>  4

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 Phe 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 Phe Leu Thr Arg 
                725                 730                 735     


Asn Leu 
        


<210>  5
<211>  2241
<212>  DNA
<213>  artificial sequence

<220>
<223>  AAV8 capsid coding (nucleotide) sequence with EYH modification 
       showing 7 additional amino acids (EYHHYNK) being inserted after 
       position 590 as well as adjacent changes

<400>  5
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc       60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac      120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac      180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac      240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt      300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag      360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct      420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc      480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca      540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga      600

cctaatacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggcgccgac      660

ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc      720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa      780

atctccaacg ggacatcggg aggagccacc aacgacaaca cctacttcgg ctacagcacc      840

ccctgggggt attttgactt taacagattc cactgccact tttcaccacg tgactggcag      900

cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac      960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc     1020

agcaccatcc aggtgtttac ggactcggag taccagctgc cgtacgttct cggctctgcc     1080

caccagggct gcctgcctcc gttcccggcg gacgtgttca tgattcccca gtacggctac     1140

ctaacactca acaacggtag tcaggccgtg ggacgctcct ccttctactg cctggaatac     1200

tttccttcgc agatgctgag aaccggcaac aacttccagt ttacttacac cttcgaggac     1260

gtgcctttcc acagcagcta cgcccacagc cagagcttgg accggctgat gaatcctctg     1320

attgaccagt acctgtacta cttgtctcgg actcaaacaa caggaggcac ggcaaatacg     1380

cagactctgg gcttcagcca aggtgggcct aatacaatgg ccaatcaggc aaagaactgg     1440

ctgccaggac cctgttaccg ccaacaacgc gtctcaacga caaccgggca aaacaacaat     1500

agcaactttg cctggactgc tgggaccaaa taccatctga atggaagaaa ttcattggct     1560

aatcctggca tcgctatggc aacacacaaa gacgacgagg agcgtttttt tcccagtaac     1620

gggatcctga tttttggcaa acaaaatgct gccagagaca atgcggatta cagcgatgtc     1680

atgctcacca gcgaggaaga aatcaaaacc actaaccctg tggctacaga ggaatacggt     1740

atcgtggcag ataacttgca gggacaacga gaataccacc actacaacaa agcacaagca     1800

gcacaaattg gaactgtcaa cagccagggg gccttacccg gtatggtctg gcagaaccgg     1860

gacgtgtacc tgcagggtcc catctgggcc aagattcctc acacggacgg caacttccac     1920

ccgtctccgc tgatgggcgg ctttggcctg aaacatcctc cgcctcagat cctgatcaag     1980

aacacgcctg tacctgcgga tcctccgacc accttcaacc agtcaaagct gaactctttc     2040

atcacgcaat acagcaccgg acaggtcagc gtggaaattg aatgggagct gcagaaggaa     2100

aacagcaagc gctggaaccc cgagatccag tacacctcca actactacaa atctacaagt     2160

gtggactttg ctgttaatac agaaggcgtg tactctgaac cccgccccat tggcacccgt     2220

tacctcaccc gtaatctgta a                                               2241


<210>  6
<211>  743
<212>  PRT
<213>  artificial sequence

<220>
<223>  AAV8 capsid amino acid sequence with EYH modification showing 7 
       additional amino acids (EYHHYNK) being inserted after position 
       590, as well as adjacent changes

<400>  6

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 Gly Gln Arg Glu Tyr 
            580                 585                 590         


His His Tyr Asn Lys Ala Gln Ala Ala Gln Ile Gly Thr Val Asn Ser 
        595                 600                 605             


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


Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His 
625                 630                 635                 640 


Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln 
                645                 650                 655     


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


Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln 
        675                 680                 685             


Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg 
    690                 695                 700                 


Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser 
705                 710                 715                 720 


Val Asp Phe Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro 
                725                 730                 735     


Ile Gly Thr Arg Tyr Leu Thr 
            740             


<210>  7
<211>  2241
<212>  DNA
<213>  artificial sequence

<220>
<223>  AAV8 capsid coding (nucleotide) sequence dual modifications: (1) 
       Tyr447 and Tyr 733 mutated to Phe residues (2) with EYH 
       modification showing 7 additional amino acids (EYHHYNK) being 
       inserted after position 590, as well as adjacent changes

<400>  7
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc       60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac      120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac      180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac      240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt      300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag      360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct      420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc      480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca      540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga      600

cctaatacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggcgccgac      660

ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc      720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa      780

atctccaacg ggacatcggg aggagccacc aacgacaaca cctacttcgg ctacagcacc      840

ccctgggggt attttgactt taacagattc cactgccact tttcaccacg tgactggcag      900

cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac      960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc     1020

agcaccatcc aggtgtttac ggactcggag taccagctgc cgtacgttct cggctctgcc     1080

caccagggct gcctgcctcc gttcccggcg gacgtgttca tgattcccca gtacggctac     1140

ctaacactca acaacggtag tcaggccgtg ggacgctcct ccttctactg cctggaatac     1200

tttccttcgc agatgctgag aaccggcaac aacttccagt ttacttacac cttcgaggac     1260

gtgcctttcc acagcagcta cgcccacagc cagagcttgg accggctgat gaatcctctg     1320

attgaccagt acctgtactt cttgtctcgg actcaaacaa caggaggcac ggcaaatacg     1380

cagactctgg gcttcagcca aggtgggcct aatacaatgg ccaatcaggc aaagaactgg     1440

ctgccaggac cctgttaccg ccaacaacgc gtctcaacga caaccgggca aaacaacaat     1500

agcaactttg cctggactgc tgggaccaaa taccatctga atggaagaaa ttcattggct     1560

aatcctggca tcgctatggc aacacacaaa gacgacgagg agcgtttttt tcccagtaac     1620

gggatcctga tttttggcaa acaaaatgct gccagagaca atgcggatta cagcgatgtc     1680

atgctcacca gcgaggaaga aatcaaaacc actaaccctg tggctacaga ggaatacggt     1740

atcgtggcag ataacttgca gggacaacga gaataccacc actacaacaa agcacaagca     1800

gcacaaattg gaactgtcaa cagccagggg gccttacccg gtatggtctg gcagaaccgg     1860

gacgtgtacc tgcagggtcc catctgggcc aagattcctc acacggacgg caacttccac     1920

ccgtctccgc tgatgggcgg ctttggcctg aaacatcctc cgcctcagat cctgatcaag     1980

aacacgcctg tacctgcgga tcctccgacc accttcaacc agtcaaagct gaactctttc     2040

atcacgcaat acagcaccgg acaggtcagc gtggaaattg aatgggagct gcagaaggaa     2100

aacagcaagc gctggaaccc cgagatccag tacacctcca actactacaa atctacaagt     2160

gtggactttg ctgttaatac agaaggcgtg tactctgaac cccgccccat tggcacccgt     2220

ttcctcaccc gtaatctgta a                                               2241


<210>  8
<211>  743
<212>  PRT
<213>  artificial sequence

<220>
<223>  AAV8 capsid amino acid sequence dual modifications: (1) Tyr447 
       and Tyr 733 mutated to Phe residues (2) with EYH modification 
       showing seven additional amino acids (EYHHYNK) being inserted 
       after position 590, as well as adjacent changes

<400>  8

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 Phe 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 Gly Gln Arg Glu Tyr 
            580                 585                 590         


His His Tyr Asn Lys Ala Gln Ala Ala Gln Ile Gly Thr Val Asn Ser 
        595                 600                 605             


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


Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His 
625                 630                 635                 640 


Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln 
                645                 650                 655     


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


Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln 
        675                 680                 685             


Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg 
    690                 695                 700                 


Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser 
705                 710                 715                 720 


Val Asp Phe Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro 
                725                 730                 735     


Ile Gly Thr Arg Phe Leu Thr 
            740             


<210>  9
<211>  34
<212>  DNA
<213>  artificial sequence

<220>
<223>  Remains of pGL3 polylinker

<400>  9
ggtaccgagc tcttacgcgt gctagcccct gcag                                   34


<210>  10
<211>  145
<212>  DNA
<213>  artificial sequence

<220>
<223>  LT ITR (Inverted Terminal Repeat)

<400>  10
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc       60

cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg      120

gccaactcca tcactagggg ttcct                                            145


<210>  11
<211>  32
<212>  DNA
<213>  artificial sequence

<220>
<223>  Sequence between ITRs

<400>  11
gcggccgcat gcatagatct acgcgtctcg ag                                     32


<210>  12
<211>  2972
<212>  DNA
<213>  artificial sequence

<220>
<223>  RT ITR (Inverted Terminal Repeat) plus remains of pGL3

<400>  12
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag agagggagtg gccaactgca ggaattcgga tccgtcgacc gatgcccttg      180

agagccttca acccagtcag ctccttccgg tgggcgcggg gcatgactat cgtcgccgca      240

cttatgactg tcttctttat catgcaactc gtaggacagg tgccggcagc gctcttccgc      300

ttcctcgctc actgactcgc tgcgctcggt cgttcggctg cggcgagcgg tatcagctca      360

ctcaaaggcg gtaatacggt tatccacaga atcaggggat aacgcaggaa agaacatgtg      420

agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca      480

taggctccgc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa      540

cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg tgcgctctcc      600

tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg gaagcgtggc      660

gctttctcaa tgctcacgct gtaggtatct cagttcggtg taggtcgttc gctccaagct      720

gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg gtaactatcg      780

tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca ctggtaacag      840

gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt ggcctaacta      900

cggctacact agaaggacag tatttggtat ctgcgctctg ctgaagccag ttaccttcgg      960

aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg gtggtttttt     1020

tgtttgcaag cagcagatta cgcgcagaaa aaaaggatct caagaagatc ctttgatctt     1080

ttctacgggg tctgacgctc agtggaacga aaactcacgt taagggattt tggtcatgag     1140

attatcaaaa aggatcttca cctagatcct tttaaattaa aaatgaagtt ttaaatcaat     1200

ctaaagtata tatgagtaaa cttggtctga cagttaccaa tgcttaatca gtgaggcacc     1260

tatctcagcg atctgtctat ttcgttcatc catagttgcc tgactccccg tcgtgtagat     1320

aactacgata cgggagggct taccatctgg ccccagtgct gcaatgatac cgcgagaccc     1380

acgctcaccg gctccagatt tatcagcaat aaaccagcca gccggaaggg ccgagcgcag     1440

aagtggtcct gcaactttat ccgcctccat ccagtctatt aattgttgcc gggaagctag     1500

agtaagtagt tcgccagtta atagtttgcg caacgttgtt gccattgcta caggcatcgt     1560

ggtgtcacgc tcgtcgtttg gtatggcttc attcagctcc ggttcccaac gatcaaggcg     1620

agttacatga tcccccatgt tgtgcaaaaa agcggttagc tccttcggtc ctccgatcgt     1680

tgtcagaagt aagttggccg cagtgttatc actcatggtt atggcagcac tgcataattc     1740

tcttactgtc atgccatccg taagatgctt ttctgtgact ggtgagtact caaccaagtc     1800

attctgagaa tagtgtatgc ggcgaccgag ttgctcttgc ccggcgtcaa tacgggataa     1860

taccgcgcca catagcagaa ctttaaaagt gctcatcatt ggaaaacgtt cttcggggcg     1920

aaaactctca aggatcttac cgctgttgag atccagttcg atgtaaccca ctcgtgcacc     1980

caactgatct tcagcatctt ttactttcac cagcgtttct gggtgagcaa aaacaggaag     2040

gcaaaatgcc gcaaaaaagg gaataagggc gacacggaaa tgttgaatac tcatactctt     2100

cctttttcaa tattattgaa gcatttatca gggttattgt ctcatgagcg gatacatatt     2160

tgaatgtatt tagaaaaata aacaaatagg ggttccgcgc acatttcccc gaaaagtgcc     2220

acctgacgcg ccctgtagcg gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt     2280

gaccgctaca cttgccagcg ccctagcgcc cgctcctttc gctttcttcc cttcctttct     2340

cgccacgttc gccggctttc cccgtcaagc tctaaatcgg gggctccctt tagggttccg     2400

atttagtgct ttacggcacc tcgaccccaa aaaacttgat tagggtgatg gttcacgtag     2460

tgggccatcg ccctgataga cggtttttcg ccctttgacg ttggagtcca cgttctttaa     2520

tagtggactc ttgttccaaa ctggaacaac actcaaccct atctcggtct attcttttga     2580

tttataaggg attttgccga tttcggccta ttggttaaaa aatgagctga tttaacaaaa     2640

atttaacgcg aattttaaca aaatattaac gtttacaatt tcccattcgc cattcaggct     2700

gcgcaactgt tgggaagggc gatcggtgcg ggcctcttcg ctattacgcc agcccaagct     2760

accatgataa gtaagtaata ttaaggtacg ggaggtactt ggagcggccg caataaaata     2820

tctttatttt cattacatct gtgtgttggt tttttgtgtg aatcgatagt actaacatac     2880

gctctccatc aaaacaaaac gaaacaaaac aaactagcaa aataggctgt ccccagtgca     2940

agtgcaggtg ccagaacatt tctctatcga ta                                   2972


<210>  13
<211>  7
<212>  PRT
<213>  artificial sequence

<220>
<223>  7-amino acid peptide that can be inserted into AAV capsid 
       sequence

<400>  13

Glu Tyr His His Tyr Asn Lys 
1               5           


<210>  14
<211>  27
<212>  DNA
<213>  artificial sequence

<220>
<223>  Upstream primer to generate Lox-1 promoter

<400>  14
atatgcatct ttcttatttg ggggaag                                           27


<210>  15
<211>  30
<212>  DNA
<213>  artificial sequence

<220>
<223>  Downstream primer to generate Lox-1 promoter

<400>  15
atacgcgtac taaaaatatg tgagcttctg                                        30


