                         SEQUENCE LISTING

<110>  INSERM
 
<120>  METHODS OF EXPRESSING A POLYNUCLEOTIDE OF INTEREST IN THE CONE 
       PHOTORECEPTORS OF A SUBJECT COMPRISING THE INTRAVITREAL DELIVERY 
       OF A THERAPEUTICALLY EFFECTIVE AMOUNT OF A RECOMBINANT 
       AAV2-DERIVED VECTOR

<130>  BIO16491 DALKARA / MC

<160>  5     

<170>  PatentIn version 3.3

<210>  1
<211>  742
<212>  PRT
<213>  Artificial

<220>
<223>  VP1 capsid of the recombinant AAV2-derived vector

<400>  1

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 Val Leu Glu Pro 
        115                 120                 125             


Leu Gly Leu Val Glu Glu Pro Val 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 Leu Gly Gln Pro Pro 
            180                 185                 190         


Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser 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 Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr 
            260                 265                 270         


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


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


Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val 
305                 310                 315                 320 


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


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


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


Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser 
    370                 375                 380                 


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


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


Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg 
            420                 425                 430         


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


Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln 
    450                 455                 460                 


Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly 
465                 470                 475                 480 


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


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


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


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


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


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


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


Thr Arg Pro Ala Arg Gln Ala Ala Thr Ala Asp Val Asn Thr Gln Gly 
        595                 600                 605             


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


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


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


Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Ser Thr Thr Phe Ser Ala 
            660                 665                 670         


Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser 
        675                 680                 685             


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


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


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


Thr Arg Tyr Leu Thr Arg 
            740         


<210>  2
<211>  1724
<212>  DNA
<213>  Artificial

<220>
<223>  pR1.7 promoter

<400>  2
ggaggctgag gggtggggaa agggcatggg tgtttcatga ggacagagct tccgtttcat     60

gcaatgaaaa gagtttggag acggatggtg gtgactggac tatacactta cacacggtag    120

cgatggtaca ctttgtatta tgtatatttt accacgatct ttttaaagtg tcaaaggcaa    180

atggccaaat ggttccttgt cctatagctg tagcagccat cggctgttag tgacaaagcc    240

cctgagtcaa gatgacagca gcccccataa ctcctaatcg gctctcccgc gtggagtcat    300

ttaggagtag tcgcattaga gacaagtcca acatctaatc ttccaccctg gccagggccc    360

cagctggcag cgagggtggg agactccggg cagagcagag ggcgctgaca ttggggcccg    420

gcctggcttg ggtccctctg gcctttcccc aggggccctc tttccttggg gctttcttgg    480

gccgccactg ctcccgctcc tctcccccca tcccaccccc tcaccccctc gttcttcata    540

tccttctcta gtgctccctc cactttcatc cacccttctg caagagtgtg ggaccacaaa    600

tgagttttca cctggcctgg ggacacacgt gcccccacag gtgctgagtg actttctagg    660

acagtaatct gctttaggct aaaatgggac ttgatcttct gttagcccta atcatcaatt    720

agcagagccg gtgaaggtgc agaacctacc gcctttccag gcctcctccc acctctgcca    780

cctccactct ccttcctggg atgtgggggc tggcacacgt gtggcccagg gcattggtgg    840

gattgcactg agctgggtca ttagcgtaat cctggacaag ggcagacagg gcgagcggag    900

ggccagctcc ggggctcagg caaggctggg ggcttccccc agacacccca ctcctcctct    960

gctggacccc cacttcatag ggcacttcgt gttctcaaag ggcttccaaa tagcatggtg   1020

gccttggatg cccagggaag cctcagagtt gcttatctcc ctctagacag aaggggaatc   1080

tcggtcaaga gggagaggtc gccctgttca aggccaccca gccagctcat ggcggtaatg   1140

ggacaaggct ggccagccat cccaccctca gaagggaccc ggtggggcag gtgatctcag   1200

aggaggctca cttctgggtc tcacattctt ggatccggtt ccaggcctcg gccctaaata   1260

gtctccctgg gctttcaaga gaaccacatg agaaaggagg attcgggctc tgagcagttt   1320

caccacccac cccccagtct gcaaatcctg acccgtgggt ccacctgccc caaaggcgga   1380

cgcaggacag tagaagggaa cagagaacac ataaacacag agagggccac agcggctccc   1440

acagtcaccg ccaccttcct ggcggggatg ggtggggcgt ctgagtttgg ttcccagcaa   1500

atccctctga gccgcccttg cgggctcgcc tcaggagcag gggagcaaga ggtgggagga   1560

ggaggtctaa gtcccaggcc caattaagag atcaggtagt gtagggtttg ggagctttta   1620

aggtgaagag gcccgggctg atcccacagg ccagtataaa gcgccgtgac cctcaggtga   1680

tgcgccaggg ccggctgccg tcggggacag ggctttccat agcc                    1724


<210>  3
<211>  552
<212>  PRT
<213>  Artificial

<220>
<223>  Jaws-GFP= Halo57 +2 mutations + KGC + GFP + ER2

<400>  3

Met Thr Ala Val Ser Thr Thr Ala Thr Thr Val Leu Gln Ala Thr Gln 
1               5                   10                  15      


Ser Asp Val Leu Gln Glu Ile Gln Ser Asn Phe Leu Leu Asn Ser Ser 
            20                  25                  30          


Ile Trp Val Asn Ile Ala Leu Ala Gly Val Val Ile Leu Leu Phe Val 
        35                  40                  45              


Ala Met Gly Arg Asp Leu Glu Ser Pro Arg Ala Lys Leu Ile Trp Val 
    50                  55                  60                  


Ala Thr Met Leu Val Pro Leu Val Ser Ile Ser Ser Tyr Ala Gly Leu 
65                  70                  75                  80  


Ala Ser Gly Leu Thr Val Gly Phe Leu Gln Met Pro Pro Gly His Ala 
                85                  90                  95      


Leu Ala Gly Gln Glu Val Leu Ser Pro Trp Gly Arg Tyr Leu Thr Trp 
            100                 105                 110         


Thr Phe Ser Thr Pro Met Ile Leu Leu Ala Leu Gly Leu Leu Ala Asp 
        115                 120                 125             


Thr Asp Ile Ala Ser Leu Phe Thr Ala Ile Thr Met Asp Ile Gly Met 
    130                 135                 140                 


Cys Val Thr Gly Leu Ala Ala Ala Leu Ile Thr Ser Ser His Leu Leu 
145                 150                 155                 160 


Arg Trp Val Phe Tyr Gly Ile Ser Cys Ala Phe Phe Val Ala Val Leu 
                165                 170                 175     


Tyr Val Leu Leu Val Gln Trp Pro Ala Asp Ala Glu Ala Ala Gly Thr 
            180                 185                 190         


Ser Glu Ile Phe Gly Thr Leu Arg Ile Leu Thr Val Val Leu Trp Leu 
        195                 200                 205             


Gly Tyr Pro Ile Leu Phe Ala Leu Gly Ser Glu Gly Val Ala Leu Leu 
    210                 215                 220                 


Ser Val Gly Val Thr Ser Trp Gly Tyr Ser Gly Leu Asp Ile Leu Ala 
225                 230                 235                 240 


Lys Tyr Val Phe Ala Phe Leu Leu Leu Arg Trp Val Ala Ala Asn Glu 
                245                 250                 255     


Gly Thr Val Ser Gly Ser Gly Met Gly Ile Gly Ser Gly Gly Ala Ala 
            260                 265                 270         


Pro Ala Asp Asp Arg Pro Val Val Lys Ser Arg Ile Thr Ser Glu Gly 
        275                 280                 285             


Glu Tyr Ile Pro Leu Asp Gln Ile Asp Ile Asn Val Ala Pro Ala Gly 
    290                 295                 300                 


Ala Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu 
305                 310                 315                 320 


Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly 
                325                 330                 335     


Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile 
            340                 345                 350         


Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr 
        355                 360                 365             


Leu Thr Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys 
    370                 375                 380                 


Gln His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu 
385                 390                 395                 400 


Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu 
                405                 410                 415     


Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly 
            420                 425                 430         


Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr 
        435                 440                 445             


Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn 
    450                 455                 460                 


Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser 
465                 470                 475                 480 


Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly 
                485                 490                 495     


Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu 
            500                 505                 510         


Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe 
        515                 520                 525             


Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys Val 
    530                 535                 540                 


Ala Phe Cys Tyr Glu Asn Glu Val 
545                 550         


<210>  4
<211>  314
<212>  PRT
<213>  Artificial

<220>
<223>  Jaws = Halo57 + 2 mutations + KGC + ER2

<400>  4

Met Thr Ala Val Ser Thr Thr Ala Thr Thr Val Leu Gln Ala Thr Gln 
1               5                   10                  15      


Ser Asp Val Leu Gln Glu Ile Gln Ser Asn Phe Leu Leu Asn Ser Ser 
            20                  25                  30          


Ile Trp Val Asn Ile Ala Leu Ala Gly Val Val Ile Leu Leu Phe Val 
        35                  40                  45              


Ala Met Gly Arg Asp Leu Glu Ser Pro Arg Ala Lys Leu Ile Trp Val 
    50                  55                  60                  


Ala Thr Met Leu Val Pro Leu Val Ser Ile Ser Ser Tyr Ala Gly Leu 
65                  70                  75                  80  


Ala Ser Gly Leu Thr Val Gly Phe Leu Gln Met Pro Pro Gly His Ala 
                85                  90                  95      


Leu Ala Gly Gln Glu Val Leu Ser Pro Trp Gly Arg Tyr Leu Thr Trp 
            100                 105                 110         


Thr Phe Ser Thr Pro Met Ile Leu Leu Ala Leu Gly Leu Leu Ala Asp 
        115                 120                 125             


Thr Asp Ile Ala Ser Leu Phe Thr Ala Ile Thr Met Asp Ile Gly Met 
    130                 135                 140                 


Cys Val Thr Gly Leu Ala Ala Ala Leu Ile Thr Ser Ser His Leu Leu 
145                 150                 155                 160 


Arg Trp Val Phe Tyr Gly Ile Ser Cys Ala Phe Phe Val Ala Val Leu 
                165                 170                 175     


Tyr Val Leu Leu Val Gln Trp Pro Ala Asp Ala Glu Ala Ala Gly Thr 
            180                 185                 190         


Ser Glu Ile Phe Gly Thr Leu Arg Ile Leu Thr Val Val Leu Trp Leu 
        195                 200                 205             


Gly Tyr Pro Ile Leu Phe Ala Leu Gly Ser Glu Gly Val Ala Leu Leu 
    210                 215                 220                 


Ser Val Gly Val Thr Ser Trp Gly Tyr Ser Gly Leu Asp Ile Leu Ala 
225                 230                 235                 240 


Lys Tyr Val Phe Ala Phe Leu Leu Leu Arg Trp Val Ala Ala Asn Glu 
                245                 250                 255     


Gly Thr Val Ser Gly Ser Gly Met Gly Ile Gly Ser Gly Gly Ala Ala 
            260                 265                 270         


Pro Ala Asp Asp Arg Pro Val Val Lys Ser Arg Ile Thr Ser Glu Gly 
        275                 280                 285             


Glu Tyr Ile Pro Leu Asp Gln Ile Asp Ile Asn Val Ala Pro Ala Gly 
    290                 295                 300                 


Ala Val Ala Phe Cys Tyr Glu Asn Glu Val 
305                 310                 


<210>  5
<211>  300
<212>  PRT
<213>  Artificial

<220>
<223>  Halo57 + 2 mutations + KGC

<400>  5

Met Thr Ala Val Ser Thr Thr Ala Thr Thr Val Leu Gln Ala Thr Gln 
1               5                   10                  15      


Ser Asp Val Leu Gln Glu Ile Gln Ser Asn Phe Leu Leu Asn Ser Ser 
            20                  25                  30          


Ile Trp Val Asn Ile Ala Leu Ala Gly Val Val Ile Leu Leu Phe Val 
        35                  40                  45              


Ala Met Gly Arg Asp Leu Glu Ser Pro Arg Ala Lys Leu Ile Trp Val 
    50                  55                  60                  


Ala Thr Met Leu Val Pro Leu Val Ser Ile Ser Ser Tyr Ala Gly Leu 
65                  70                  75                  80  


Ala Ser Gly Leu Thr Val Gly Phe Leu Gln Met Pro Pro Gly His Ala 
                85                  90                  95      


Leu Ala Gly Gln Glu Val Leu Ser Pro Trp Gly Arg Tyr Leu Thr Trp 
            100                 105                 110         


Thr Phe Ser Thr Pro Met Ile Leu Leu Ala Leu Gly Leu Leu Ala Asp 
        115                 120                 125             


Thr Asp Ile Ala Ser Leu Phe Thr Ala Ile Thr Met Asp Ile Gly Met 
    130                 135                 140                 


Cys Val Thr Gly Leu Ala Ala Ala Leu Ile Thr Ser Ser His Leu Leu 
145                 150                 155                 160 


Arg Trp Val Phe Tyr Gly Ile Ser Cys Ala Phe Phe Val Ala Val Leu 
                165                 170                 175     


Tyr Val Leu Leu Val Gln Trp Pro Ala Asp Ala Glu Ala Ala Gly Thr 
            180                 185                 190         


Ser Glu Ile Phe Gly Thr Leu Arg Ile Leu Thr Val Val Leu Trp Leu 
        195                 200                 205             


Gly Tyr Pro Ile Leu Phe Ala Leu Gly Ser Glu Gly Val Ala Leu Leu 
    210                 215                 220                 


Ser Val Gly Val Thr Ser Trp Gly Tyr Ser Gly Leu Asp Ile Leu Ala 
225                 230                 235                 240 


Lys Tyr Val Phe Ala Phe Leu Leu Leu Arg Trp Val Ala Ala Asn Glu 
                245                 250                 255     


Gly Thr Val Ser Gly Ser Gly Met Gly Ile Gly Ser Gly Gly Ala Ala 
            260                 265                 270         


Pro Ala Asp Asp Arg Pro Val Val Lys Ser Arg Ile Thr Ser Glu Gly 
        275                 280                 285             


Glu Tyr Ile Pro Leu Asp Gln Ile Asp Ile Asn Val 
    290                 295                 300 


