Listado de secuencias <110> LLC "ANABION" <120> Ácido nucleico optimizado por codones que codifica la proteína del factor de coagulación IX, y uso del mismo <150> RU2021105703 <151> 2021-03-05 <160> 17 <170> BiSSAP 1.3.6 <210> 1 <211> 461 <212> PRT <213> Secuencia natural <220> <223> Secuencia de aminoácidos de la proteína del factor de coagulación IX recombinante con la mutación R338L <400> 1 Met Gln Arg Val Asn Met Ile Met Ala Glu Ser Pro Gly Leu Ile Thr 1. 5 10 15 Ile Cys Leu Leu Gly Tyr Leu Leu Ser Ala Glu Cys Thr Val Phe Leu 20 25 30 Asp His Glu Asn Ala Asn Lys Ile Leu Asn Arg Pro Lys Arg Tyr Asn 35 40 45 Ser Gly Lys Leu Glu Glu Phe Val Gln Gly Asn Leu Glu Arg Glu Cys 50 55 60 Met Glu Glu Lys Cys Ser Phe Glu Glu Ala Arg Glu Val Phe Glu Asn 65 70 75 80 Thr Glu Arg Thr Thr Glu Phe Trp Lys Gln Tyr Val Asp Gly Asp Gln 85 90 95 Cys Glu Ser Asn Pro Cys Leu Asn Gly Gly Ser Cys Lys Asp Asp Ile 100 105 110 Asn Ser Tyr Glu Cys Trp Cys Pro Phe Gly Phe Glu Gly Lys Asn Cys 115 120 125 Glu Leu Asp Val Thr Cys Asn Ile Lys Asn Gly Arg Cys Glu Gln Phe 130 135 140 Cys Lys Asn Ser Ala Asp Asn Lys Val Val Cys Ser Cys Thr Glu Gly 145 150 155 160 Tyr Arg Leu Ala Glu Asn Gln Lys Ser Cys Glu Pro Ala Val Pro Phe 165 170 175 Pro Cys Gly Arg Val Ser Val Ser Gln Thr Ser Lys Leu Thr Arg Ala 180 185 190 Glu Thr Val Phe Pro Asp Val Asp Tyr Val Asn Ser Thr Glu Ala Glu 195 200 205 Thr Ile Leu Asp Asn Ile Thr Gln Ser Thr Gln Ser Phe Asn Asp Phe 210 215 220 Thr Arg Val Val Gly Gly Glu Asp Ala Lys Pro Gly Gln Phe Pro Trp 225 230 235 240 Gln Val Val Leu Asn Gly Lys Val Asp Ala Phe Cys Gly Gly Ser Ile 245 250 255 Val Asn Glu Lys Trp Ile Val Thr Ala Ala His Cys Val Glu Thr Gly 260 265 270 Val Lys Ile Thr Val Val Ala Gly Glu His Asn Ile Glu Glu Thr Glu 275 280 285 His Thr Glu Gln Lys Arg Asn Val Ile Arg Ile Ile Pro His His Asn 290 295 300 Tyr Asn Ala Ala Ile Asn Lys Tyr Asn His Asp Ile Ala Leu Leu Glu 305 310 315 320 Leu Asp Glu Pro Leu Val Leu Asn Ser Tyr Val Thr Pro Ile Cys Ile 325 330 335 Ala Asp Lys Glu Tyr Thr Asn Ile Phe Leu Lys Phe Gly Ser Gly Tyr 340 345 350 Val Ser Gly Trp Gly Arg Val Phe His Lys Gly Arg Ser Ala Leu Val 355 360 365 Leu Gln Tyr Leu Arg Val Pro Leu Val Asp Arg Ala Thr Cys Leu Leu 370 375 380 Ser Thr Lys Phe Thr Ile Tyr Asn Asn Met Phe Cys Ala Gly Phe His 385 390 395 400 Glu Gly Gly Arg Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro His Val 405 410 415 Thr Glu Val Glu Gly Thr Ser Phe Leu Thr Gly Ile Ile Ser Trp Gly 420 425 430 Glu Glu Cys Ala Met Lys Gly Lys Tyr Gly Ile Tyr Thr Lys Val Ser 435 440 445 Arg Tyr Val Asn Trp Ile Lys Glu Lys Thr Lys Leu Thr 450 455 460 <210> 2 <211> 1383 <212> ADN <213> Secuencia artificial <220> <223> Ácido nucleico optimizado por codones que codifica el factor IX de coagulación sanguínea recombinante (variante hFIXco-v1) <400> 2 atgcagcggg tcaacatgat catggcggag tcgccgggcc tgatcacgat ctgcctcctc 60 gggtacctgc tctccgccga gtgcaccgtg ttcctggacc acgagaacgc caacaagatc 120 ctcaaccggc ccaagcgcta caactccggc aagctggagg agttcgtgca ggggaacctc 180 gagcgcgagt gcatggagga gaagtgctcg ttcgaggagg cgcgggaggt gttcgagaac 240 accgagcgca ccacggagtt ctggaagcag tacgtggacg gggaccagtg cgagtcgaac 300 ccgtgcctca acggggggtc gtgcaaggac gacatcaact cgtacgagtg ctggtgcccc 360 ttcggcttcg agggcaagaa ctgcgagctg gacgtgacct gcaacatcaa gaacgggcgc 420 tgcgagcagt tctgcaagaa cagcgccgac aacaaggtgg tctgctcctg caccgagggg 480 taccgcctcg cggagaacca gaagtcctgc gagccggccg tgcccttccc ctgcggccgc 540 gtgtccgtca gccagacgtc gaagctgacg cgcgccgaga ccgtcttccc ggacgtggac 600 tacgtgaact cgacggaggc cgagaccatc ctggacaaca tcacccagag cacccagtcc 660 ttcaacgact tcacgcgggt ggtcggcggc gaggacgcca agcccgggca gttcccgtgg 720 caggtcgtcc tcaacgggaa ggtcgacgcg ttctgcggcg ggagcatcgt gaacgagaag 780 tggatcgtga ccgccgcgca ctgcgtcgag acgggcgtga agatcaccgt ggtggccggg 840 gagcacaaca tcgaggagac ggagcacacc gagcagaagc ggaacgtgat ccgcatcatc 900 ccgcaccaca actacaacgc cgccatcaac aagtacaacc acgacatcgc gctcctcgag 960 ctggacgagc cgctggtcct caactcctac gtcacgccga tctgcatcgc cgacaaggag 1020 tacacgaaca tcttcctgaa gttcgggagc ggctacgtct cgggctgggg ccgcgtgttc 1080 cacaaggggc gcagcgcgct cgtgctccag tacctgcggg tccccctggt cgaccgcgcg 1140 acctgcctcc tctccacgaa gttcacgatc tacaacaaca tgttctgcgc ggggttccac 1200 gagggcggcc gggacagctg ccagggcgac agcgggggcc cgcacgtgac ggaggtggag 1260 ggcacgagct tcctgaccgg gatcatctcg tggggcgagg agtgcgcgat gaaggggaag 1320 tacggcatct acaccaaggt cagccggtac gtgaactgga tcaaggagaa gacgaagctg 1380 acg 1383 <210> 3 <211> 3122 <212> ADN <213> Secuencia artificial <220> <223> casete de expresión con el gen del factor de coagulación IX recombinante optimizado por el codón (variante AAV5-hFIXco-v1) <400> 3 cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt 60 ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120 aggggttcct gcggccgcac gcgtgccgcc accatggtcg agcttgggct gcaggtcgag 180 ggcactggga ggatgttgag taagatggaa aactactgat gacccttgca gagacagagt 240 attaggacat gtttgaacag gggccggcga tcagcaggta gctctagagg atccccgtct 300 gtctgcacat ttcgtagagc gagtgttccg atactctaat ctccctaggc aaggttcata 360 tttgtgtagg ttacttattc tccttttgtt gactaagtca ataatcagaa tcagcaggtt 420 tggagtcagc ttggcaggga tcagcagcct gggttggaag gagggggtat aaaagcccct 480 tcaccaggag aagccgtcac acagatccac aagctcctga caggaagctc taggtgactc 540 tcttaaggta gcctccgcgg attcgaatcc cggccgggaa cggtgcattg gaacgcggat 600 tccccgtgcc aagagtgacg taagtaccgc ctatagagtc tataggccca caaaaaatgc 660 tttcttcttt taatatactt ttttgtttat cttatttcta atactttccc taatctcttt 720 ctttcagggc aataatgata caatgtatca tgcctctttg caccattcta aagaataaca 780 gtgataattt ctgggttaag gcaatagcaa tatttctgca tataaatatt tctgcatata 840 aattgtaact gatgtaagag gtttcatatt gctaatagca gctacaatcc agctaccatt 900 ctgcttttat tttatggttg ggataaggct ggattattct gagtccaagc taggcccttt 960 tgctaatcat gttcatacct cttatcttcc tcccacagct cctgggcaac gtgctggtct 1020 gtgtgctggc ccatcacttt ggcaaagaat tgggattcga acatcgatat gcagcgggtc 1080 aacatgatca tggcggagtc gccgggcctg atcacgatct gcctcctcgg gtacctgctc 1140 tccgccgagt gcaccgtgtt cctggaccac gagaacgcca acaagatcct caaccggccc 1200 aagcgctaca actccggcaa gctggaggag ttcgtgcagg ggaacctcga gcgcgagtgc 1260 atggaggaga agtgctcgtt cgaggaggcg cgggaggtgt tcgagaacac cgagcgcacc 1320 acggagttct ggaagcagta cgtggacggg gaccagtgcg agtcgaaccc gtgcctcaac 1380 ggggggtcgt gcaaggacga catcaactcg tacgagtgct ggtgcccctt cggcttcgag 1440 ggcaagaact gcgagctgga cgtgacctgc aacatcaaga acgggcgctg cgagcagttc 1500 tgcaagaaca gcgccgacaa caaggtggtc tgctcctgca ccgaggggta ccgcctcgcg 1560 gagaaccaga agtcctgcga gccggccgtg cccttcccct gcggccgcgt gtccgtcagc 1620 cagacgtcga agctgacgcg cgccgagacc gtcttcccgg acgtggacta cgtgaactcg 1680 acggaggccg agaccatcct ggacaacatc acccagagca cccagtcctt caacgacttc 1740 acgcgggtgg tcggcggcga ggacgccaag cccgggcagt tcccgtggca ggtcgtcctc 1800 aacgggaagg tcgacgcgtt ctgcggcggg agcatcgtga acgagaagtg gatcgtgacc 1860 gccgcgcact gcgtcgagac gggcgtgaag atcaccgtgg tggccgggga gcacaacatc 1920 gaggagacgg agcacaccga gcagaagcgg aacgtgatcc gcatcatccc gcaccacaac 1980 tacaacgccg ccatcaacaa gtacaaccac gacatcgcgc tcctcgagct ggacgagccg 2040 ctggtcctca actcctacgt cacgccgatc tgcatcgccg acaaggagta cacgaacatc 2100 ttcctgaagt tcgggagcgg ctacgtctcg ggctggggcc gcgtgttcca caaggggcgc 2160 agcgcgctcg tgctccagta cctgcgggtc cccctggtcg accgcgcgac ctgcctcctc 2220 tccacgaagt tcacgatcta caacaacatg ttctgcgcgg ggttccacga gggcggccgg 2280 gacagctgcc agggcgacag cgggggcccg cacgtgacgg aggtggaggg cacgagcttc 2340 ctgaccggga tcatctcgtg gggcgaggag tgcgcgatga aggggaagta cggcatctac 2400 accaaggtca gccggtacgt gaactggatc aaggagaaga cgaagctgac gtgatgaaga 2460 tctacgggtg gcatccctgt gacccctccc cagtgcccct cctggccctg gaagttgcca 2520 ctccagtgcc caccagcctt gtcctaataa aattaagttg catcattttg tctgactagg 2580 tgtccttcta taatattatg gggtggaggg gggtggtatg gagcaagggg caagttggga 2640 agacaacctg tagggcctgc ggggtctatt gggaaccaag ctggagtgca gtggcacaat 2700 cttggctcac tgcaatctcc gcctcctggg ttcaagcgat tctcctgcct cagcctcccg 2760 agttgttggg attccaggca tgcatgacca ggctcagcta atttttgttt ttttggtaga 2820 gacggggttt caccatattg gccaggctgg tctccaactc ctaatctcag gtgatctacc 2880 caccttggcc tcccaaattg ctgggattac aggcgtgaac cactgctccc ttccctgtcc 2940 ttctgatttt gtaggtaacc acgtgcggac cgagcggccg caggaacccc tagtgatgga 3000 gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc 3060 ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca 3120 gg 3122 <210> 4 <211> 1383 <212> ADN <213> Secuencia artificial <220> <223> Ácido nucleico optimizado en codones que codifica el factor IX de coagulación sanguínea recombinante (variante hFIXco-v2) <400> 4 atgcagcggg tgaacatgat catggccgag tccccaggcc tgattaccat ctgtctgctg 60 ggctacctgc tgagcgccga atgcaccgtg tttctggacc acgagaacgc caacaagatc 120 ctgaaccgcc ctaagcggta caactccggc aagctggagg agtttgtgca gggcaatctg 180 gagcgggagt gtatggagga gaagtgcagc ttcgaggagg ccagggaggt gttcgagaac 240 accgagagga ccaccgagtt ctggaagcag tatgtggacg gcgaccagtg cgagtctaat 300 ccttgtctga atggcgggag ctgcaaggac gacatcaaca gctacgagtg ctggtgccct 360 ttcggcttcg agggcaagaa ttgcgagctg gacgtgacct gcaacatcaa gaacggccgg 420 tgtgagcagt tctgcaagaa cagcgccgac aacaaggtgg tgtgctcctg caccgaggga 480 tacaggctgg ccgagaatca gaagagctgt gagcccgccg tgccattccc ctgtggcaga 540 gtgtctgtga gccagaccag caagctgacc agagccgaga ccgtgtttcc agacgtggac 600 tacgtgaaca gcaccgaggc cgagaccatc ctggataata tcacccagtc cacccagagc 660 ttcaacgact tcaccagagt ggtgggaggc gaggatgcca agccaggaca gtttccctgg 720 caggtggtgc tgaatggcaa ggtggacgcc ttctgcggag gcagcatcgt gaacgagaag 780 tggattgtga ccgcagccca ctgcgtggag actggcgtga agattaccgt ggtcgccggc 840 gagcacaata tcgaagagac cgagcacacc gagcagaagc gcaacgtgat ccggatcatc 900 cctcaccaca actacaacgc agccatcaac aagtacaacc acgacatcgc cctgctggag 960 ctggacgagc cactggtgct gaactcttac gtgaccccta tctgcatcgc cgacaaggag 1020 tacaccaaca tcttcctgaa gttcggcagc ggctacgtga gcggatgggg cagagtgttt 1080 cacaagggca ggagcgccct ggtgctgcag tatctgagag tgccactggt ggacagagct 1140 acctgcctgc tgagcaccaa gttcaccatc tacaacaaca tgttctgcgc cggcttccac 1200 gaggggggaa gagactcttg ccagggcgat tccggcggac cacacgtgac cgaagtggag 1260 ggcaccagct tcctgaccgg catcatctcc tggggcgagg aatgcgccat gaagggcaag 1320 tacggcatct acaccaaggt gagcaggtac gtgaactgga tcaaggagaa gaccaagctg 1380 acc 1383 <210> 5 <211> 3123 <212> ADN <213> Secuencia artificial <220> <223> casete de expresión con un gen optimizado en codones para el factor IX de coagulación sanguínea recombinante (variante AAV5-hFIXco-v2) <400> 5 cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt 60 ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120 aggggttcct gcggccgcac gcgtgccgcc accatggtcg agcttgggct gcaggtcgag 180 ggcactggga ggatgttgag taagatggaa aactactgat gacccttgca gagacagagt 240 attaggacat gtttgaacag gggccggcga tcagcaggta gctctagagg atccccgtct 300 gtctgcacat ttcgtagagc gagtgttccg atactctaat ctccctaggc aaggttcata 360 tttgtgtagg ttacttattc tccttttgtt gactaagtca ataatcagaa tcagcaggtt 420 tggagtcagc ttggcaggga tcagcagcct gggttggaag gagggggtat aaaagcccct 480 tcaccaggag aagccgtcac acagatccac aagctcctga caggaagctc taggtgactc 540 tcttaaggta gcctccgcgg attcgaatcc cggccgggaa cggtgcattg gaacgcggat 600 tccccgtgcc aagagtgacg taagtaccgc ctatagagtc tataggccca caaaaaatgc 660 tttcttcttt taatatactt ttttgtttat cttatttcta atactttccc taatctcttt 720 ctttcagggc aataatgata caatgtatca tgcctctttg caccattcta aagaataaca 780 gtgataattt ctgggttaag gcaatagcaa tatttctgca tataaatatt tctgcatata 840 aattgtaact gatgtaagag gtttcatatt gctaatagca gctacaatcc agctaccatt 900 ctgcttttat tttatggttg ggataaggct ggattattct gagtccaagc taggcccttt 960 tgctaatcat gttcatacct cttatcttcc tcccacagct cctgggcaac gtgctggtct 1020 gtgtgctggc ccatcacttt ggcaaagaat tgggattcga acatcgatat aaatgcagcg 1080 ggtgaacatg atcatggccg agtccccagg cctgattacc atctgtctgc tgggctacct 1140 gctgagcgcc gaatgcaccg tgtttctgga ccacgagaac gccaacaaga tcctgaaccg 1200 ccctaagcgg tacaactccg gcaagctgga ggagtttgtg cagggcaatc tggagcggga 1260 gtgtatggag gagaagtgca gcttcgagga ggccagggag gtgttcgaga acaccgagag 1320 gaccaccgag ttctggaagc agtatgtgga cggcgaccag tgcgagtcta atccttgtct 1380 gaatggcggg agctgcaagg acgacatcaa cagctacgag tgctggtgcc ctttcggctt 1440 cgagggcaag aattgcgagc tggacgtgac ctgcaacatc aagaacggcc ggtgtgagca 1500 gttctgcaag aacagcgccg acaacaaggt ggtgtgctcc tgcaccgagg gatacaggct 1560 ggccgagaat cagaagagct gtgagcccgc cgtgccattc ccctgtggca gagtgtctgt 1620 gagccagacc agcaagctga ccagagccga gaccgtgttt ccagacgtgg actacgtgaa 1680 cagcaccgag gccgagacca tcctggataa tatcacccag tccacccaga gcttcaacga 1740 cttcaccaga gtggtgggag gcgaggatgc caagccagga cagtttccct ggcaggtggt 1800 gctgaatggc aaggtggacg ccttctgcgg aggcagcatc gtgaacgaga agtggattgt 1860 gaccgcagcc cactgcgtgg agactggcgt gaagattacc gtggtcgccg gcgagcacaa 1920 tatcgaagag accgagcaca ccgagcagaa gcgcaacgtg atccggatca tccctcacca 1980 caactacaac gcagccatca acaagtacaa ccacgacatc gccctgctgg agctggacga 2040 gccactggtg ctgaactctt acgtgacccc tatctgcatc gccgacaagg agtacaccaa 2100 catcttcctg aagttcggca gcggctacgt gagcggatgg ggcagagtgt ttcacaaggg 2160 caggagcgcc ctggtgctgc agtatctgag agtgccactg gtggacagag ctacctgcct 2220 gctgagcacc aagttcacca tctacaacaa catgttctgc gccggcttcc acgagggggg 2280 aagagactct tgccagggcg attccggcgg accacacgtg accgaagtgg agggcaccag 2340 cttcctgacc ggcatcatct cctggggcga ggaatgcgcc atgaagggca agtacggcat 2400 ctacaccaag gtgagcaggt acgtgaactg gatcaaggag aagaccaagc tgacctgaag 2460 atctacgggt ggcatccctg tgacccctcc ccagtgcccc tcctggccct ggaagttgcc 2520 actccagtgc ccaccagcct tgtcctaata aaattaagtt gcatcatttt gtctgactag 2580 gtgtccttct ataatattat ggggtggagg ggggtggtat ggagcaaggg gcaagttggg 2640 aagacaacct gtagggcctg cggggtctat tgggaaccaa gctggagtgc agtggcacaa 2700 tcttggctca ctgcaatctc cgcctcctgg gttcaagcga ttctcctgcc tcagcctccc 2760 gagttgttgg gattccaggc atgcatgacc aggctcagct aatttttgtt tttttggtag 2820 agacggggtt tcaccatatt ggccaggctg gtctccaact cctaatctca ggtgatctac 2880 ccaccttggc ctcccaaatt gctgggatta caggcgtgaa ccactgctcc cttccctgtc 2940 cttctgattt tgtaggtaac cacgtgcgga ccgagcggcc gcaggaaccc ctagtgatgg 3000 agttggccac tccctctctg cgcgctcgct cgctcactga ggccgggcga ccaaaggtcg 3060 cccgacgccc gggctttgcc cgggcggcct cagtgagcga gcgagcgcgc agctgcctgc 3120 agg 3123 <210> 6 <211> 130 <212> ADN <213> Secuencia artificial <220> <223> ITR (repeticiones terminales invertidas) de lado izquierdo (primera) <400> 6 cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt 60 ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120 aggggttcct 130 <210> 7 <211> 372 <212> ADN <213> Secuencia natural <220> <223> Secuencia promotora de la TTR (promotor de la transtiretina) <400> 7 tcgagcttgg gctgcaggtc gagggcactg ggaggatgtt gagtaagatg gaaaactact 60 gatgaccctt gcagagacag agtattagga catgtttgaa caggggccgg cgatcagcag 120 gtagctctag aggatccccg tctgtctgca catttcgtag agcgagtgtt ccgatactct 180 aatctcccta ggcaaggttc atatttgtgt aggttactta ttctcctttt gttgactaag 240 tcaataatca gaatcagcag gtttggagtc agcttggcag ggatcagcag cctgggttgg 300 aaggaggggg tataaaagcc ccttcaccag gagaagccgt cacacagatc cacaagctcc 360 tgacaggaag ct 372 <210> 8 <211> 493 <212> ADN <213> Secuencia natural <220> <223> intrón del gen hBG1 (un fragmento del gen de la β globina humana que lleva el intrón) <400> 8 cgaatcccgg ccgggaacgg tgcattggaa cgcggattcc ccgtgccaag agtgacgtaa 60 gtaccgccta tagagtctat aggcccacaa aaaatgcttt cttcttttaa tatacttttt 120 tgtttatctt atttctaata ctttccctaa tctctttctt tcagggcaat aatgatacaa 180 tgtatcatgc ctctttgcac cattctaaag aataacagtg ataatttctg ggttaaggca 240 atagcaatat ttctgcatat aaatatttct gcatataaat tgtaactgat gtaagaggtt 300 tcatattgct aatagcagct acaatccagc taccattctg cttttatttt atggttggga 360 taaggctgga ttattctgag tccaagctag gcccttttgc taatcatgtt catacctctt 420 atcttcctcc cacagctcct gggcaacgtg ctggtctgtg tgctggccca tcactttggc 480 aaagaattgg gat 493 <210> 9 <211> 479 <212> ADN <213> Secuencia natural <220> <223> Señal de poliadenilación hGH1 (señal de poliadenilación del gen de la hormona de crecimiento humana) <400> 9 acgggtggca tccctgtgac ccctccccag tgcccctcct ggccctggaa gttgccactc 60 cagtgcccac cagccttgtc ctaataaaat taagttgcat cattttgtct gactaggtgt 120 ccttctataa tattatgggg tggagggggg tggtatggag caaggggcaa gttgggaaga 180 caacctgtag ggcctgcggg gtctattggg aaccaagctg gagtgcagtg gcacaatctt 240 ggctcactgc aatctccgcc tcctgggttc aagcgattct cctgcctcag cctcccgagt 300 tgttgggatt ccaggcatgc atgaccaggc tcagctaatt tttgtttttt tggtagagac 360 ggggtttcac catattggcc aggctggtct ccaactccta atctcaggtg atctacccac 420 cttggcctcc caaattgctg ggattacagg cgtgaaccac tgctcccttc cctgtcctt 479 <210> 10 <211> 141 <212> ADN <213> Secuencia artificial <220> <223> ITR derecho (segundo) <400> 10 aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg 60 ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc 120 gagcgcgcag ctgcctgcag g 141 <210> 11 <211> 724 <212> PRT <213> Secuencia natural <220> <223> Secuencia natural de la proteína VP1 de la cápside del AAV5 de tipo salvaje <400> 11 Met Ser Phe Val Asp His Pro Pro Asp Trp Leu Glu Glu Val Gly Glu 1. 5 10 15 Gly Leu Arg Glu Phe Leu Gly Leu Glu Ala Gly Pro Pro Lys Pro Lys 20 25 30 Pro Asn Gln Gln His Gln Asp Gln Ala Arg Gly Leu Val Leu Pro Gly 35 40 45 Tyr Asn Tyr Leu Gly Pro Gly Asn Gly Leu Asp Arg Gly Glu Pro Val 50 55 60 Asn Arg Ala Asp Glu Val Ala Arg Glu His Asp Ile Ser Tyr Asn Glu 65 70 75 80 Gln Leu Glu Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala Asp 85 90 95 Ala Glu Phe Gln Glu Lys Leu Ala Asp Asp Thr Ser Phe Gly Gly Asn 100 105 110 Leu Gly Lys Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro Phe 115 120 125 Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Thr Gly Lys Arg Ile 130 135 140 Asp Asp His Phe Pro Lys Arg Lys Lys Ala Arg Thr Glu Glu Asp Ser 145 150 155 160 Lys Pro Ser Thr Ser Ser Asp Ala Glu Ala Gly Pro Ser Gly Ser Gln 165 170 175 Gln Leu Gln Ile Pro Ala Gln Pro Ala Ser Ser Leu Gly Ala Asp Thr 180 185 190 Met Ser Ala Gly Gly Gly Gly Pro Leu Gly Asp Asn Asn Gln Gly Ala 195 200 205 Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys Asp Ser Thr Trp 210 215 220 Met Gly Asp Arg Val Val Thr Lys Ser Thr Arg Thr Trp Val Leu Pro 225 230 235 240 Ser Tyr Asn Asn His Gln Tyr Arg Glu Ile Lys Ser Gly Ser Val Asp 245 250 255 Gly Ser Asn Ala Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 260 265 270 Phe Asp Phe Asn Arg Phe His Ser His Trp Ser Pro Arg Asp Trp Gln 275 280 285 Arg Leu Ile Asn Asn Tyr Trp Gly Phe Arg Pro Arg Ser Leu Arg Val 290 295 300 Lys Ile Phe Asn Ile Gln Val Lys Glu Val Thr Val Gln Asp Ser Thr 305 310 315 320 Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp 325 330 335 Asp Asp Tyr Gln Leu Pro Tyr Val Val Gly Asn Gly Thr Glu Gly Cys 340 345 350 Leu Pro Ala Phe Pro Pro Gln Val Phe Thr Leu Pro Gln Tyr Gly Tyr 355 360 365 Ala Thr Leu Asn Arg Asp Asn Thr Glu Asn Pro Thr Glu Arg Ser Ser 370 375 380 Phe Phe Cys Leu Glu Tyr Phe Pro Ser Lys Met Leu Arg Thr Gly Asn 385 390 395 400 Asn Phe Glu Phe Thr Tyr Asn Phe Glu Glu Val Pro Phe His Ser Ser 405 410 415 Phe Ala Pro Ser Gln Asn Leu Phe Lys Leu Ala Asn Pro Leu Val Asp 420 425 430 Gln Tyr Leu Tyr Arg Phe Val Ser Thr Asn Asn Thr Gly Gly Val Gln 435 440 445 Phe Asn Lys Asn Leu Ala Gly Arg Tyr Ala Asn Thr Tyr Lys Asn Trp 450 455 460 Phe Pro Gly Pro Met Gly Arg Thr Gln Gly Trp Asn Leu Gly Ser Gly 465 470 475 480 Val Asn Arg Ala Ser Val Ser Ala Phe Ala Thr Thr Asn Arg Met Glu 485 490 495 Leu Glu Gly Ala Ser Tyr Gln Val Pro Pro Gln Pro Asn Gly Met Thr 500 505 510 Asn Asn Leu Gln Gly Ser Asn Thr Tyr Ala Leu Glu Asn Thr Met Ile 515 520 525 Phe Asn Ser Gln Pro Ala Asn Pro Gly Thr Thr Ala Thr Tyr Leu Glu 530 535 540 Gly Asn Met Leu Ile Thr Ser Glu Ser Glu Thr Gln Pro Val Asn Arg 545 550 555 560 Val Ala Tyr Asn Val Gly Gly Gln Met Ala Thr Asn Asn Gln Ser Ser 565 570 575 Thr Thr Ala Pro Ala Thr Gly Thr Tyr Asn Leu Gln Glu Ile Val Pro 580 585 590 Gly Ser Val Trp Met Glu Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp 595 600 605 Ala Lys Ile Pro Glu Thr Gly Ala His Phe His Pro Ser Pro Ala Met 610 615 620 Gly Gly Phe Gly Leu Lys His Pro Pro Pro Met Met Leu Ile Lys Asn 625 630 635 640 Thr Pro Val Pro Gly Asn Ile Thr Ser Phe Ser Asp Val Pro Val Ser 645 650 655 Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Thr Val Glu Met Glu 660 665 670 Trp Glu Leu Lys Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln 675 680 685 Tyr Thr Asn Asn Tyr Asn Asp Pro Gln Phe Val Asp Phe Ala Pro Asp 690 695 700 Ser Thr Gly Glu Tyr Arg Thr Thr Arg Pro Ile Gly Thr Arg Tyr Leu 705 710 715 720 Thr Arg Pro Leu <210> 12 <211> 588 <212> PRT <213> Secuencia natural <220> <223> Secuencia natural de la proteína VP2 de la cápside del AAV5 de tipo salvaje <400> 12 Thr Ala Pro Thr Gly Lys Arg Ile Asp Asp His Phe Pro Lys Arg Lys 1. 5 10 15 Lys Ala Arg Thr Glu Glu Asp Ser Lys Pro Ser Thr Ser Ser Asp Ala 20 25 30 Glu Ala Gly Pro Ser Gly Ser Gln Gln Leu Gln Ile Pro Ala Gln Pro 35 40 45 Ala Ser Ser Leu Gly Ala Asp Thr Met Ser Ala Gly Gly Gly Gly Pro 50 55 60 Leu Gly Asp Asn Asn Gln Gly Ala Asp Gly Val Gly Asn Ala Ser Gly 65 70 75 80 Asp Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Val Thr Lys 85 90 95 Ser Thr Arg Thr Trp Val Leu Pro Ser Tyr Asn Asn His Gln Tyr Arg 100 105 110 Glu Ile Lys Ser Gly Ser Val Asp Gly Ser Asn Ala Asn Ala Tyr Phe 115 120 125 Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Ser 130 135 140 His Trp Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Tyr Trp Gly 145 150 155 160 Phe Arg Pro Arg Ser Leu Arg Val Lys Ile Phe Asn Ile Gln Val Lys 165 170 175 Glu Val Thr Val Gln Asp Ser Thr Thr Thr Ile Ala Asn Asn Leu Thr 180 185 190 Ser Thr Val Gln Val Phe Thr Asp Asp Asp Tyr Gln Leu Pro Tyr Val 195 200 205 Val Gly Asn Gly Thr Glu Gly Cys Leu Pro Ala Phe Pro Pro Gln Val 210 215 220 Phe Thr Leu Pro Gln Tyr Gly Tyr Ala Thr Leu Asn Arg Asp Asn Thr 225 230 235 240 Glu Asn Pro Thr Glu Arg Ser Ser Phe Phe Cys Leu Glu Tyr Phe Pro 245 250 255 Ser Lys Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Thr Tyr Asn Phe 260 265 270 Glu Glu Val Pro Phe His Ser Ser Phe Ala Pro Ser Gln Asn Leu Phe 275 280 285 Lys Leu Ala Asn Pro Leu Val Asp Gln Tyr Leu Tyr Arg Phe Val Ser 290 295 300 Thr Asn Asn Thr Gly Gly Val Gln Phe Asn Lys Asn Leu Ala Gly Arg 305 310 315 320 Tyr Ala Asn Thr Tyr Lys Asn Trp Phe Pro Gly Pro Met Gly Arg Thr 325 330 335 Gln Gly Trp Asn Leu Gly Ser Gly Val Asn Arg Ala Ser Val Ser Ala 340 345 350 Phe Ala Thr Thr Asn Arg Met Glu Leu Glu Gly Ala Ser Tyr Gln Val 355 360 365 Pro Pro Gln Pro Asn Gly Met Thr Asn Asn Leu Gln Gly Ser Asn Thr 370 375 380 Tyr Ala Leu Glu Asn Thr Met Ile Phe Asn Ser Gln Pro Ala Asn Pro 385 390 395 400 Gly Thr Thr Ala Thr Tyr Leu Glu Gly Asn Met Leu Ile Thr Ser Glu 405 410 415 Ser Glu Thr Gln Pro Val Asn Arg Val Ala Tyr Asn Val Gly Gly Gln 420 425 430 Met Ala Thr Asn Asn Gln Ser Ser Thr Thr Ala Pro Ala Thr Gly Thr 435 440 445 Tyr Asn Leu Gln Glu Ile Val Pro Gly Ser Val Trp Met Glu Arg Asp 450 455 460 Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro Glu Thr Gly Ala 465 470 475 480 His Phe His Pro Ser Pro Ala Met Gly Gly Phe Gly Leu Lys His Pro 485 490 495 Pro Pro Met Met Leu Ile Lys Asn Thr Pro Val Pro Gly Asn Ile Thr 500 505 510 Ser Phe Ser Asp Val Pro Val Ser Ser Phe Ile Thr Gln Tyr Ser Thr 515 520 525 Gly Gln Val Thr Val Glu Met Glu Trp Glu Leu Lys Lys Glu Asn Ser 530 535 540 Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Asn Asn Tyr Asn Asp Pro 545 550 555 560 Gln Phe Val Asp Phe Ala Pro Asp Ser Thr Gly Glu Tyr Arg Thr Thr 565 570 575 Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 580 585 <210> 13 <211> 532 <212> PRT <213> Secuencia natural <220> <223> Secuencia natural de la proteína VP3 de la cápside del AAV5 de tipo salvaje <400> 13 Met Ser Ala Gly Gly Gly Gly Pro Leu Gly Asp Asn Asn Gln Gly Ala 1. 5 10 15 Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys Asp Ser Thr Trp 20 25 30 Met Gly Asp Arg Val Val Thr Lys Ser Thr Arg Thr Trp Val Leu Pro 35 40 45 Ser Tyr Asn Asn His Gln Tyr Arg Glu Ile Lys Ser Gly Ser Val Asp 50 55 60 Gly Ser Asn Ala Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 65 70 75 80 Phe Asp Phe Asn Arg Phe His Ser His Trp Ser Pro Arg Asp Trp Gln 85 90 95 Arg Leu Ile Asn Asn Tyr Trp Gly Phe Arg Pro Arg Ser Leu Arg Val 100 105 110 Lys Ile Phe Asn Ile Gln Val Lys Glu Val Thr Val Gln Asp Ser Thr 115 120 125 Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp 130 135 140 Asp Asp Tyr Gln Leu Pro Tyr Val Val Gly Asn Gly Thr Glu Gly Cys 145 150 155 160 Leu Pro Ala Phe Pro Pro Gln Val Phe Thr Leu Pro Gln Tyr Gly Tyr 165 170 175 Ala Thr Leu Asn Arg Asp Asn Thr Glu Asn Pro Thr Glu Arg Ser Ser 180 185 190 Phe Phe Cys Leu Glu Tyr Phe Pro Ser Lys Met Leu Arg Thr Gly Asn 195 200 205 Asn Phe Glu Phe Thr Tyr Asn Phe Glu Glu Val Pro Phe His Ser Ser 210 215 220 Phe Ala Pro Ser Gln Asn Leu Phe Lys Leu Ala Asn Pro Leu Val Asp 225 230 235 240 Gln Tyr Leu Tyr Arg Phe Val Ser Thr Asn Asn Thr Gly Gly Val Gln 245 250 255 Phe Asn Lys Asn Leu Ala Gly Arg Tyr Ala Asn Thr Tyr Lys Asn Trp 260 265 270 Phe Pro Gly Pro Met Gly Arg Thr Gln Gly Trp Asn Leu Gly Ser Gly 275 280 285 Val Asn Arg Ala Ser Val Ser Ala Phe Ala Thr Thr Asn Arg Met Glu 290 295 300 Leu Glu Gly Ala Ser Tyr Gln Val Pro Pro Gln Pro Asn Gly Met Thr 305 310 315 320 Asn Asn Leu Gln Gly Ser Asn Thr Tyr Ala Leu Glu Asn Thr Met Ile 325 330 335 Phe Asn Ser Gln Pro Ala Asn Pro Gly Thr Thr Ala Thr Tyr Leu Glu 340 345 350 Gly Asn Met Leu Ile Thr Ser Glu Ser Glu Thr Gln Pro Val Asn Arg 355 360 365 Val Ala Tyr Asn Val Gly Gly Gln Met Ala Thr Asn Asn Gln Ser Ser 370 375 380 Thr Thr Ala Pro Ala Thr Gly Thr Tyr Asn Leu Gln Glu Ile Val Pro 385 390 395 400 Gly Ser Val Trp Met Glu Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp 405 410 415 Ala Lys Ile Pro Glu Thr Gly Ala His Phe His Pro Ser Pro Ala Met 420 425 430 Gly Gly Phe Gly Leu Lys His Pro Pro Pro Met Met Leu Ile Lys Asn 435 440 445 Thr Pro Val Pro Gly Asn Ile Thr Ser Phe Ser Asp Val Pro Val Ser 450 455 460 Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Thr Val Glu Met Glu 465 470 475 480 Trp Glu Leu Lys Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln 485 490 495 Tyr Thr Asn Asn Tyr Asn Asp Pro Gln Phe Val Asp Phe Ala Pro Asp 500 505 510 Ser Thr Gly Glu Tyr Arg Thr Thr Arg Pro Ile Gly Thr Arg Tyr Leu 515 520 525 Thr Arg Pro Leu 530 <210> 14 <211> 724 <212> PRT <213> Secuencia artificial <220> <223> proteína VP1 de la cápside de AAV5 modificada que incluye las sustituciones S2A y T711S <400> 14 Met Ala Phe Val Asp His Pro Pro Asp Trp Leu Glu Glu Val Gly Glu 1. 5 10 15 Gly Leu Arg Glu Phe Leu Gly Leu Glu Ala Gly Pro Pro Lys Pro Lys 20 25 30 Pro Asn Gln Gln His Gln Asp Gln Ala Arg Gly Leu Val Leu Pro Gly 35 40 45 Tyr Asn Tyr Leu Gly Pro Gly Asn Gly Leu Asp Arg Gly Glu Pro Val 50 55 60 Asn Arg Ala Asp Glu Val Ala Arg Glu His Asp Ile Ser Tyr Asn Glu 65 70 75 80 Gln Leu Glu Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala Asp 85 90 95 Ala Glu Phe Gln Glu Lys Leu Ala Asp Asp Thr Ser Phe Gly Gly Asn 100 105 110 Leu Gly Lys Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro Phe 115 120 125 Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Thr Gly Lys Arg Ile 130 135 140 Asp Asp His Phe Pro Lys Arg Lys Lys Ala Arg Thr Glu Glu Asp Ser 145 150 155 160 Lys Pro Ser Thr Ser Ser Asp Ala Glu Ala Gly Pro Ser Gly Ser Gln 165 170 175 Gln Leu Gln Ile Pro Ala Gln Pro Ala Ser Ser Leu Gly Ala Asp Thr 180 185 190 Met Ser Ala Gly Gly Gly Gly Pro Leu Gly Asp Asn Asn Gln Gly Ala 195 200 205 Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys Asp Ser Thr Trp 210 215 220 Met Gly Asp Arg Val Val Thr Lys Ser Thr Arg Thr Trp Val Leu Pro 225 230 235 240 Ser Tyr Asn Asn His Gln Tyr Arg Glu Ile Lys Ser Gly Ser Val Asp 245 250 255 Gly Ser Asn Ala Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 260 265 270 Phe Asp Phe Asn Arg Phe His Ser His Trp Ser Pro Arg Asp Trp Gln 275 280 285 Arg Leu Ile Asn Asn Tyr Trp Gly Phe Arg Pro Arg Ser Leu Arg Val 290 295 300 Lys Ile Phe Asn Ile Gln Val Lys Glu Val Thr Val Gln Asp Ser Thr 305 310 315 320 Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp 325 330 335 Asp Asp Tyr Gln Leu Pro Tyr Val Val Gly Asn Gly Thr Glu Gly Cys 340 345 350 Leu Pro Ala Phe Pro Pro Gln Val Phe Thr Leu Pro Gln Tyr Gly Tyr 355 360 365 Ala Thr Leu Asn Arg Asp Asn Thr Glu Asn Pro Thr Glu Arg Ser Ser 370 375 380 Phe Phe Cys Leu Glu Tyr Phe Pro Ser Lys Met Leu Arg Thr Gly Asn 385 390 395 400 Asn Phe Glu Phe Thr Tyr Asn Phe Glu Glu Val Pro Phe His Ser Ser 405 410 415 Phe Ala Pro Ser Gln Asn Leu Phe Lys Leu Ala Asn Pro Leu Val Asp 420 425 430 Gln Tyr Leu Tyr Arg Phe Val Ser Thr Asn Asn Thr Gly Gly Val Gln 435 440 445 Phe Asn Lys Asn Leu Ala Gly Arg Tyr Ala Asn Thr Tyr Lys Asn Trp 450 455 460 Phe Pro Gly Pro Met Gly Arg Thr Gln Gly Trp Asn Leu Gly Ser Gly 465 470 475 480 Val Asn Arg Ala Ser Val Ser Ala Phe Ala Thr Thr Asn Arg Met Glu 485 490 495 Leu Glu Gly Ala Ser Tyr Gln Val Pro Pro Gln Pro Asn Gly Met Thr 500 505 510 Asn Asn Leu Gln Gly Ser Asn Thr Tyr Ala Leu Glu Asn Thr Met Ile 515 520 525 Phe Asn Ser Gln Pro Ala Asn Pro Gly Thr Thr Ala Thr Tyr Leu Glu 530 535 540 Gly Asn Met Leu Ile Thr Ser Glu Ser Glu Thr Gln Pro Val Asn Arg 545 550 555 560 Val Ala Tyr Asn Val Gly Gly Gln Met Ala Thr Asn Asn Gln Ser Ser 565 570 575 Thr Thr Ala Pro Ala Thr Gly Thr Tyr Asn Leu Gln Glu Ile Val Pro 580 585 590 Gly Ser Val Trp Met Glu Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp 595 600 605 Ala Lys Ile Pro Glu Thr Gly Ala His Phe His Pro Ser Pro Ala Met 610 615 620 Gly Gly Phe Gly Leu Lys His Pro Pro Pro Met Met Leu Ile Lys Asn 625 630 635 640 Thr Pro Val Pro Gly Asn Ile Thr Ser Phe Ser Asp Val Pro Val Ser 645 650 655 Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Thr Val Glu Met Glu 660 665 670 Trp Glu Leu Lys Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln 675 680 685 Tyr Thr Asn Asn Tyr Asn Asp Pro Gln Phe Val Asp Phe Ala Pro Asp 690 695 700 Ser Thr Gly Glu Tyr Arg Ser Thr Arg Pro Ile Gly Thr Arg Tyr Leu 705 710 715 720 Thr Arg Pro Leu <210> 15 <211> 588 <212> PRT <213> Secuencia artificial <220> <223> proteína VP2 de la cápside de AAV5 modificada que incluye la sustitución T575S <400> 15 Thr Ala Pro Thr Gly Lys Arg Ile Asp Asp His Phe Pro Lys Arg Lys 1. 5 10 15 Lys Ala Arg Thr Glu Glu Asp Ser Lys Pro Ser Thr Ser Ser Asp Ala 20 25 30 Glu Ala Gly Pro Ser Gly Ser Gln Gln Leu Gln Ile Pro Ala Gln Pro 35 40 45 Ala Ser Ser Leu Gly Ala Asp Thr Met Ser Ala Gly Gly Gly Gly Pro 50 55 60 Leu Gly Asp Asn Asn Gln Gly Ala Asp Gly Val Gly Asn Ala Ser Gly 65 70 75 80 Asp Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Val Thr Lys 85 90 95 Ser Thr Arg Thr Trp Val Leu Pro Ser Tyr Asn Asn His Gln Tyr Arg 100 105 110 Glu Ile Lys Ser Gly Ser Val Asp Gly Ser Asn Ala Asn Ala Tyr Phe 115 120 125 Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Ser 130 135 140 His Trp Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Tyr Trp Gly 145 150 155 160 Phe Arg Pro Arg Ser Leu Arg Val Lys Ile Phe Asn Ile Gln Val Lys 165 170 175 Glu Val Thr Val Gln Asp Ser Thr Thr Thr Ile Ala Asn Asn Leu Thr 180 185 190 Ser Thr Val Gln Val Phe Thr Asp Asp Asp Tyr Gln Leu Pro Tyr Val 195 200 205 Val Gly Asn Gly Thr Glu Gly Cys Leu Pro Ala Phe Pro Pro Gln Val 210 215 220 Phe Thr Leu Pro Gln Tyr Gly Tyr Ala Thr Leu Asn Arg Asp Asn Thr 225 230 235 240 Glu Asn Pro Thr Glu Arg Ser Ser Phe Phe Cys Leu Glu Tyr Phe Pro 245 250 255 Ser Lys Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Thr Tyr Asn Phe 260 265 270 Glu Glu Val Pro Phe His Ser Ser Phe Ala Pro Ser Gln Asn Leu Phe 275 280 285 Lys Leu Ala Asn Pro Leu Val Asp Gln Tyr Leu Tyr Arg Phe Val Ser 290 295 300 Thr Asn Asn Thr Gly Gly Val Gln Phe Asn Lys Asn Leu Ala Gly Arg 305 310 315 320 Tyr Ala Asn Thr Tyr Lys Asn Trp Phe Pro Gly Pro Met Gly Arg Thr 325 330 335 Gln Gly Trp Asn Leu Gly Ser Gly Val Asn Arg Ala Ser Val Ser Ala 340 345 350 Phe Ala Thr Thr Asn Arg Met Glu Leu Glu Gly Ala Ser Tyr Gln Val 355 360 365 Pro Pro Gln Pro Asn Gly Met Thr Asn Asn Leu Gln Gly Ser Asn Thr 370 375 380 Tyr Ala Leu Glu Asn Thr Met Ile Phe Asn Ser Gln Pro Ala Asn Pro 385 390 395 400 Gly Thr Thr Ala Thr Tyr Leu Glu Gly Asn Met Leu Ile Thr Ser Glu 405 410 415 Ser Glu Thr Gln Pro Val Asn Arg Val Ala Tyr Asn Val Gly Gly Gln 420 425 430 Met Ala Thr Asn Asn Gln Ser Ser Thr Thr Ala Pro Ala Thr Gly Thr 435 440 445 Tyr Asn Leu Gln Glu Ile Val Pro Gly Ser Val Trp Met Glu Arg Asp 450 455 460 Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro Glu Thr Gly Ala 465 470 475 480 His Phe His Pro Ser Pro Ala Met Gly Gly Phe Gly Leu Lys His Pro 485 490 495 Pro Pro Met Met Leu Ile Lys Asn Thr Pro Val Pro Gly Asn Ile Thr 500 505 510 Ser Phe Ser Asp Val Pro Val Ser Ser Phe Ile Thr Gln Tyr Ser Thr 515 520 525 Gly Gln Val Thr Val Glu Met Glu Trp Glu Leu Lys Lys Glu Asn Ser 530 535 540 Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Asn Asn Tyr Asn Asp Pro 545 550 555 560 Gln Phe Val Asp Phe Ala Pro Asp Ser Thr Gly Glu Tyr Arg Ser Thr 565 570 575 Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 580 585 <210> 16 <211> 532 <212> PRT <213> Secuencia artificial <220> <223> proteína VP3 de la cápside de AAV5 modificada que incluye la sustitución T519S <400> 16 Met Ser Ala Gly Gly Gly Gly Pro Leu Gly Asp Asn Asn Gln Gly Ala 1. 5 10 15 Asp Gly Val Gly Asn Ala Ser Gly Asp Trp His Cys Asp Ser Thr Trp 20 25 30 Met Gly Asp Arg Val Val Thr Lys Ser Thr Arg Thr Trp Val Leu Pro 35 40 45 Ser Tyr Asn Asn His Gln Tyr Arg Glu Ile Lys Ser Gly Ser Val Asp 50 55 60 Gly Ser Asn Ala Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 65 70 75 80 Phe Asp Phe Asn Arg Phe His Ser His Trp Ser Pro Arg Asp Trp Gln 85 90 95 Arg Leu Ile Asn Asn Tyr Trp Gly Phe Arg Pro Arg Ser Leu Arg Val 100 105 110 Lys Ile Phe Asn Ile Gln Val Lys Glu Val Thr Val Gln Asp Ser Thr 115 120 125 Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp 130 135 140 Asp Asp Tyr Gln Leu Pro Tyr Val Val Gly Asn Gly Thr Glu Gly Cys 145 150 155 160 Leu Pro Ala Phe Pro Pro Gln Val Phe Thr Leu Pro Gln Tyr Gly Tyr 165 170 175 Ala Thr Leu Asn Arg Asp Asn Thr Glu Asn Pro Thr Glu Arg Ser Ser 180 185 190 Phe Phe Cys Leu Glu Tyr Phe Pro Ser Lys Met Leu Arg Thr Gly Asn 195 200 205 Asn Phe Glu Phe Thr Tyr Asn Phe Glu Glu Val Pro Phe His Ser Ser 210 215 220 Phe Ala Pro Ser Gln Asn Leu Phe Lys Leu Ala Asn Pro Leu Val Asp 225 230 235 240 Gln Tyr Leu Tyr Arg Phe Val Ser Thr Asn Asn Thr Gly Gly Val Gln 245 250 255 Phe Asn Lys Asn Leu Ala Gly Arg Tyr Ala Asn Thr Tyr Lys Asn Trp 260 265 270 Phe Pro Gly Pro Met Gly Arg Thr Gln Gly Trp Asn Leu Gly Ser Gly 275 280 285 Val Asn Arg Ala Ser Val Ser Ala Phe Ala Thr Thr Asn Arg Met Glu 290 295 300 Leu Glu Gly Ala Ser Tyr Gln Val Pro Pro Gln Pro Asn Gly Met Thr 305 310 315 320 Asn Asn Leu Gln Gly Ser Asn Thr Tyr Ala Leu Glu Asn Thr Met Ile 325 330 335 Phe Asn Ser Gln Pro Ala Asn Pro Gly Thr Thr Ala Thr Tyr Leu Glu 340 345 350 Gly Asn Met Leu Ile Thr Ser Glu Ser Glu Thr Gln Pro Val Asn Arg 355 360 365 Val Ala Tyr Asn Val Gly Gly Gln Met Ala Thr Asn Asn Gln Ser Ser 370 375 380 Thr Thr Ala Pro Ala Thr Gly Thr Tyr Asn Leu Gln Glu Ile Val Pro 385 390 395 400 Gly Ser Val Trp Met Glu Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp 405 410 415 Ala Lys Ile Pro Glu Thr Gly Ala His Phe His Pro Ser Pro Ala Met 420 425 430 Gly Gly Phe Gly Leu Lys His Pro Pro Pro Met Met Leu Ile Lys Asn 435 440 445 Thr Pro Val Pro Gly Asn Ile Thr Ser Phe Ser Asp Val Pro Val Ser 450 455 460 Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Thr Val Glu Met Glu 465 470 475 480 Trp Glu Leu Lys Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln 485 490 495 Tyr Thr Asn Asn Tyr Asn Asp Pro Gln Phe Val Asp Phe Ala Pro Asp 500 505 510 Ser Thr Gly Glu Tyr Arg Ser Thr Arg Pro Ile Gly Thr Arg Tyr Leu 515 520 525 Thr Arg Pro Leu 530 <210> 17 <211> 1383 <212> ADN <213> Secuencia natural <220> <223> ácido nucleico que codifica el factor de coagulación IX recombinante de tipo salvaje (hFIX-wt) con la mutación R338L <400> 17 atgcagcgcg tgaacatgat catggcagaa tcaccaggcc tcatcaccat ctgcctttta 60 ggatatctac tcagtgctga atgtacagtt tttcttgatc atgaaaacgc caacaaaatt 120 ctgaatcggc caaagaggta taattcaggt aaattggaag agtttgttca agggaacctt 180 gagagagaat gtatggaaga aaagtgtagt tttgaagaag cacgagaagt ttttgaaaac 240 actgaaagaa caactgaatt ttggaagcag tatgttgatg gagatcagtg tgagtccaat 300 ccatgtttaa atggcggcag ttgcaaggat gacattaatt cctatgaatg ttggtgtccc 360 tttggatttg aaggaaagaa ctgtgaatta gatgtaacat gtaacattaa gaatggcaga 420 tgcgagcagt tttgtaaaaa tagtgctgat aacaaggtgg tttgctcctg tactgaggga 480 tatcgacttg cagaaaacca gaagtcctgt gaaccagcag tgccatttcc atgtggaaga 540 gtttctgttt cacaaacttc taagctcacc cgtgctgaga ctgtttttcc tgatgtggac 600 tatgtaaatt ctactgaagc tgaaaccatt ttggataaca tcactcaaag cacccaatca 660 tttaatgact tcactcgggt tgttggtgga gaagatgcca aaccaggtca attcccttgg 720 caggttgttt tgaatggtaa agttgatgca ttctgtggag gctctatcgt taatgaaaaa 780 tggattgtaa ctgctgccca ctgtgttgaa actggtgtta aaattacagt tgtcgcaggt 840 gaacataata ttgaggagac agaacataca gagcaaaagc gaaatgtgat tcgaattatt 900 cctcaccaca actacaatgc agctattaat aagtacaacc atgacattgc ccttctggaa 960 ctggacgaac ccttagtgct aaacagctac gttacaccta tttgcattgc tgacaaggaa 1020 tacacgaaca tcttcctcaa atttggatct ggctatgtaa gtggctgggg aagagtcttc 1080 cacaaaggga gatcagcttt agttcttcag taccttagag ttccacttgt tgaccgagcc 1140 acatgtcttc tatctacaaa gttcaccatc tataacaaca tgttctgtgc tggcttccat 1200 gaaggaggta gagattcatg tcaaggagat agtgggggac cccatgttac tgaagtggaa 1260 gggaccagtt tcttaactgg aattattagc tggggtgaag agtgtgcaat gaaaggcaaa 1320 tatggaatat ataccaaggt atcccggtat gtcaactgga ttaaggaaaa aacaaagctc 1380 act 1383