OLIGONUCLEOTIDE COMPRISING AN INOSINE FOR TREATING DMD

Abstract

The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.

Claims

1.-19. (canceled)

20. An oligonucleotide consisting of the base sequence of SEQ ID NO: 143, wherein said oligonucleotide comprises a modification and induces skipping of exon 53 of human dystrophin pre-mRNA.

21. The oligonucleotide of claim 20, wherein at least one guanosine base is substituted with an inosine base.

22. The oligonucleotide of claim 21, wherein the oligonucleotide contains one to four inosine bases.

23. The oligonucleotide of claim 20, wherein the modification is a base and/or sugar modification.

24. The oligonucleotide of claim 23, wherein the oligonucleotide is a 2-O-methyl phosphorothioate oligonucleotide.

25. The oligonucleotide of claim 23, wherein the oligonucleotide is a peptide nucleic acid oligonucleotide.

26. The oligonucleotide of claim 23, wherein the oligonucleotide is a phosphorodiamidate morpholino oligomer oligonucleotide.

27. A pharmaceutical composition, comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.

28. A method for inducing skipping of exon 53 of human dystrophin pre-mRNA in a human subject, comprising administering the oligonucleotide of claim 1 to the subject in an amount and for a time which is effective to induce exon skipping.

29. A method for alleviating one or more symptom(s) of Duchenne Muscular Dystrophy or Becker Muscular in a human subject, comprising administering to the subject the oligonucleotide of claim 1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0152] FIG. 1. In human control myotubes, PS220 and PS305 both targeting an identical sequence within exon 45, were directly compared for relative skipping efficiencies. PS220 reproducibly induced highest levels of exon 45 skipping (up to 73%), whereas with PS305 maximum exon 45 skipping levels of up to 46% were obtained. No exon 45 skipping was observed in non-treated cells. (M: DNA size marker; NT: non-treated cells)

[0153] FIG. 2. Graph showing relative exon 45 skipping levels of inosine-containing AONs as assessed by RT-PCR analysis. In human control myotubes, a series of new AONs, all targeting exon 45 and containing one inosine for guanosine substitution were tested for relative exon 45 skipping efficiencies when compared with PS220 and PS305 (see FIG. 1). All new inosine-containing AONs were effective, albeit at variable levels (between 4% and 25%). PS220 induced highest levels of exon 45 skipping (up to 72%), whereas with PS305 maximum exon 45 skipping levels of up to 63% were obtained. No exon 45 skipping was observed in non-treated cells. (M: DNA size marker; NT: non-treated cells).

EXAMPLES

Example 1

[0154] Materials and methods

[0155] AON design was based on (partly) overlapping open secondary structures of the target exon RNA as predicted by the m-fold program, on (partly) overlapping putative SR-protein binding sites as predicted by the ESE-finder software. AONs were synthesized by Prosensa Therapeutics B.V. (Leiden, Netherlands), and contain 2-O-methyl RNA and full-length phosphorothioate (PS) backbones.

[0156] Tissue culturing, transfection and RT-PCR analysis

[0157] Myotube cultures derived from a healthy individual (human control) (examples 1, 3, and 4; exon 43, 50, 52 skipping) or a DMD patient carrying an exon 45 deletion (example 2; exon 46 skipping) were processed as described previously (Aartsma-Rus et al., Neuromuscul. Disord. 2002; 12: S71-77 and Hum Mol Genet 2003; 12(8): 907-14). For the screening of AONs, myotube cultures were transfected with 200nM for each AON (PS220 and PS305). Transfection reagent UNIFectylin (Prosensa Therapeutics BV, Netherlands) was used, with 2 l UNIFectylin per g AON. Exon skipping efficiencies were determined by nested RT-PCR analysis using primers in the exons flanking the targeted exon 45. PCR fragments were isolated from agarose gels for sequence verification. For quantification, the PCR products were analyzed using the DNA 1000 LabChip Kit on the Agilent 2100 bioanalyzer (Agilent Technologies, USA).

[0158] Results

[0159] DMD exon 45 skipping.

[0160] Two AONs, PS220 (SEQ ID NO: 76; 5-UUUGCCGCUGCCCAAUGCCAUCCUG-.sub.3) and PS305 (SEQ ID NO: 557; 5-UUUGCCICUGCCCAAUGCCAUCCUG-.sub.3) both targeting an identical sequence within exon 45, were directly compared for relative skipping efficiencies in healthy control myotube cultures. Subsequent RT-PCR and sequence analysis of isolated RNA demonstrated that both AONs were indeed capable of inducing exon 45 skipping. PS220, consisting a GCCGC stretch, reproducibly induced highest levels of exon 45 skipping (up to 73%), as shown in FIG. 1. However, PS305, which is identical to PS220 but containing an inosine for a G substitution at position 4 within that stretch is also effective and leading to exon 45 skipping levels of up to 46%. No exon 45 skipping was observed in non-treated cells (NT).

Example 2

[0161] Materials and methods

[0162] AON design was based on (partly) overlapping open secondary structures of the target exon 45 RNA as predicted by the m-fold program, on (partly) overlapping putative SR-protein binding sites as predicted by the ESE-finder software. AONs were synthesized by Prosensa Therapeutics B.V. (Leiden, Netherlands), and contain 2-O-methyl RNA , full-length phosphorothioate (PS) backbones and one inosine for guanosine substitution.

[0163] Tissue culturing, transfection and RT-PCR analysis

[0164] Myotube cultures derived from a healthy individual (human control) were processed as described previously (Aartsma-Rus et al., Neuromuscul. Disord. 2002; 12: S71-77 and Hum Mol Genet 2003; 12(8): 907-14). For the screening of AONs, myotube cultures were transfected with 200nM for each AON. Transfection reagent UNIFectylin (Prosensa Therapeutics BY, Netherlands) was used, with 2 l UNIFectylin per g AON. Exon skipping efficiencies were determined by nested RT-PCR analysis using primers in the exons flanking the targeted exon 45. PCR fragments were isolated from agarose gels for sequence verification. For quantification, the PCR products were analyzed using the DNA 1000 Lab Chip Kit on the Agilent 2100 bioanalyzer (Agilent Technologies, USA).

[0165] Results

[0166] DMD exon 45 skipping.

[0167] An additional series of AONs targeting exon 45 and containing one inosine-substitution were tested in healthy control myotube cultures for exon 45 skipping efficiencies, and directly compared to PS220 (without inosine; SEQ ID NO: 76)) and PS305 (identical sequence as PS220 but with inosine substitution; SEQ ID NO: 557). Subsequent RT-PCR and sequence analysis of isolated RNA demonstrated that all new AONs (PS309 to PS316) were capable of inducing exon 45 skipping between 4% (PS311) and 25% (PS310) as shown in FIG. 2. When compared to PS220 and PS305, PS220 induced highest levels of exon 45 skipping (up to 72%). Of the new inosine-containing AONs PS305 was most effective, showing exon 45 skipping levels of up to 63%. No exon 45 skipping was observed in non-treated cells (NT).

REFERENCES

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TABLE-US-00001 Sequencelisting DMDgeneaminoacidsequence SEQIDNO1: MLWWEEVEDCYEREDVQKKTFTKWVNAQFSKFGKQHIENLFSDLQDGRRLLDLLEGL TGQKLPKEKGSTRVHALNNVNKALRVLQNNNVDLVNIGSTDIVDGNHKLTLGLIWNIIL HWQVKNVMKNIMAGLQQTNSEKILLSWVRQSTRNYPQVNVINFVPSWSDGLALNALIH SHRPDLFDWNSVVCQQSATQRLEHAFNIARYQLGIEKLLDPEDVDITYPDKKSILMYIT SLFQVLPQQVSIEAIQEVEMLPRPPKVTKEEHFQLHHQMHYSQQITVSLAQGYERTSSP KPRFKSYAYTQAAYVTTSDPTRSPFPSQHLEAPEDKSFGSSLMESEVNLDRYQTALEEV LSWLLSAEDTLQAQGEISNDVEVVKDQFHTHEGYMMDLTAHQGRVGNILQLGSKLIGT GKLSEDEETEVQEQMNLLNSRWECLRVASMEKQSNLHRVLMDLQNQKLKELNDWLT KTEERTRKMEEEPLGPDLEDLKRQVQQHKVLQEDLEQEQVRVNSLTHMVVVVDESSG DHATAALEEQLKVLGDRWANICRWTEDRWVLLQDILLKWQRLTEEQCLFSAWLSEKE DAVNKIHTTGFKDQNEMLSSLQKLAVLKADLEKKKQSMGKLYSLKQDLLSTLKNKSVT QKTEAWLDNFARCWDNLVQKLEKSTAQISQAVTTTQPSLTQTTVMETVTTVTTREQILV KHAQEELPPPPPQKKRQITVDSEIRKRLDVDITELHSWITRSEAVLQSPEFAIFRKEGNF SDLKEKVNAIEREKAEKFRKLQDASRSAQALVEQMVNEGVNADSIKQASEQLNSRWIE FCQLLSERLNWLEYQNNIIAFYNQLQQLEQMPTTAENWLKIQPTPPSEPTAIKSQLKIC KDEVNRLSGLQPQIERLKIQSIALKEKGQGPMFLDADFVAFTNHFKQVFSDVQAREKEL QTIFDTLPPMRYQETMSAIRTWVQQSETKLSIPQLSVTDYEIMEQRLGELQALQSSLQE QQSGLYYLSTTVKEMSKKAPSEISRKYQSEFEEIEGRWKKLSSQLVEHCQKLEEQMNK LRKIQNHIQTLKKWMAEVDVFLKEEWPALGDSEILKKQLKQCRLLVSDIQTIQPSLNSV NEGGQKIKNEAEPEFASRLETELKELNTQWDHMCQQVYARKEALKGGLEKTVSLQKD LSEMHEWMTQAEEEYLERDFEYKTPDELQKAVEEMKRAKEEAQQKEAKVKLLTESV NSVIAQAPPVAQEALKKELETLTTNYQWLCTRLNGKCKTLEEVWACWHELLSYLEKAN KWLNEVEFKLKTTENIPGGAEEISEVLDSLENLMRHSEDNPNQIRILAQTLTDGGVMD ELINEELETFNSRWRELHEEAVRRQKLLEQSIQSAQETEKSLHLIQESLTFIDKQLAAYI ADKVDAAQMPQEAQKIQSDLTSHEISLEEMKKHNQGKEAAQRVLSQIDVAQKKLQDVS MKFRLFQKPANFEQRLQESKMILDEVKMHLPALETKSVEQEVVQSQLNHCVNLYKSLS EVKSEVEMVIKTGRQIVQKKQTENPKELDERVTALKLHYNELGAKVTERKQQLEKCLK LSRKMRKEMNVLTEWLAATDMELTKRSAVEGMPSNLDSEVAWGKATQKEIEKQKVH LKSITEVGEALKTVLGKKETLVEDKLSLLNSNWIAVTSRAEEWLNLLLEYQKHMETFD QNVDHITKWIIQADTLLDESEKKKPQQKEDVLKRLKAELNDIRPKVDSTRDQAANLMA NRGDHCRKLVEPQISELNHRFAAISHRIKTGKASIPLKELEQFNSDIQKLLEPLEAEIQQ GVNLKEEDFNKDMNEDNEGTVKELLQRGDNLQQRITDERKREEIKIKQQLLQTKHNA LKDLRSQRRKKALEISHQWYQYKRQADDLLKCLDDIEKKLASLPEPRDERKIKEIDREL QKKKEELNAVRRQAEGLSEDGAAMAVEPTQIQLSKRWREIESKFAQFRRLNFAQIHTV REETMMVMTEDMPLEISYVPSTYLTEITHVSQALLEVEQLLNAPDLCAKDFEDLFKQE ESLKNIKDSLQQSSGRIDIIHSKKTAALQSATPVERVKLQEALSQLDFQWEKVNKMYKD RQGRFDRSVEKWRRFHYDIKIFNQWLTEAEQFLRKTQIPENWEHAKYKWYLKELQDGI GQRQTVVRTLNATGEEIIQQSSKTDASILQEKLGSLNLRWQEVCKQLSDRKKRLEEQKN ILSEFQRDLNEFVLWLEEADNIASIPLEPGKEQQLKEKLEQVKLLVEELPLRQGILKQL NETGGPVLVSAPISPEEQDKLENKLKQTNLQWIKVSRALPEKQGEIEAQIKDLGQLEKK LEDLEEQLNHLLLWLSPIRNQLEIYNQPNQEGPFDVQETEIAVQAKQPDVEEILSKGQH LYKEKPATQPVKRKLEDLSSEWKAVNRLLQELRAKQPDLAPGLTTIGASPTQTVTLVTQ PVVTKETAISKLEMPSSLMLEVPALADFNRAWTELTDWLSLLDQVIKSQRVMVGDLEDI NEMIIKQKATMQDLEQRRPQLEELITAAQNLKNKTSNQEARTIITDRIERIQNQWDEVQ EHLQNRRQQLNEMLKDSTQWLEAKEEAEQVLGQARAKLESWKEGPYTVDAIQKKITE TKQLAKDLRQWQTNVDVANDLALKLLRDYSADDTRKVHMITENINASWRSIHKRVSER EAALEETHRLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQ WQDLQGEIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSL NIRSHLEASSDQWKRLHLSLQELLVWLQLKDDELSRQAPIGGDFPAVQKQNDVHRAFK RELKTKEPVIMSTLETVRIFLTEQPLEGLEKLYQEPRELPPEERAQNVTRLLRKQAEEV NTEWEKLNLHSADWQRKIDETLERLQELQEATDELDLKLRQAEVIKGSWQPVGDLLID SLQDHLEKVKALRGEIAPLKENVSHVNDLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQ VAVEDRVRQLHEAHRDFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHP KMTELYQSLADLNNVRFSAYRTAMKLRRLQKALCLDLLSLSAACDALDQHNLKQNDQ PMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTG IISLCKAHLEDKYRYLFKQVASSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSV RSCFQFANNKPEIEAALFLDWMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPI IGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTTSGEDVRDFAKVLKNK FRTKRYFAKHPRMGYLPVQTVLEGDNMETPVTLINFWPVDSAPASSPQLSHDDTHSRI EHYASRLAEMENSNGSYLNDSISPNESIDDEHLLIQHYCQSLNQDSPLSQPRSPAQILIS LESEERGELERILADLEEENRNLQAEYDRLKQQHEHKGLSPLPSPPEMMPTSPQSPRD AELIAEAKLLRQHKGRLEARMQILEDHNKQLESQLHRLRQLLEQPQAEAKVNGTTVSS PSTSLQRSDSSQPMLLRVVGSQTSDSMGEEDLLSPPQDTSTGLEEVMEQLNNSFPSSRG RNTPGKPMREDTM DMDGeneExon51 SEQID GUACCUCCAACAUCAAGGAAGAUGG SEQID GAGAUGGCAGUUUCCUUAGUAACCA NO2 NO39 SEQID UACCUCCAACAUCAAGGAAGAUGGC SEQID AGAUGGCAGUUUCCUUAGUAACCAC NO3 NO40 SEQID ACCUCCAACAUCAAGGAAGAUGGCA SEQID GAUGGCAGUUUCCUUAGUAACCACA NO4 NO41 SEQID CCUCCAACAUCAAGGAAGAUGGCAU SEQID AUGGCAGUUUCCUUAGUAACCACAG NO5 NO42 SEQID CUCCAACAUCAAGGAAGAUGGCAUU SEQID UGGCAGUUUCCUUAGUAACCACAGG NO6 NO43 SEQID UCCAACAUCAAGGAAGAUGGCAUUU SEQID GGCAGUUUCCUUAGUAACCACAGGU NO7 NO44 SEQID CCAACAUCAAGGAAGAUGGCAUUUC SEQID GCAGUUUCCUUAGUAACCACAGGUU NO8 NO45 SEQID CAACAUCAAGGAAGAUGGCAUUUCU SEQID CAGUUUCCUUAGUAACCACAGGUUG NO9 NO46 SEQID AACAUCAAGGAAGAUGGCAUUUCUA SEQID AGUUUCCUUAGUAACCACAGGUUGU NO10 NO47 SEQID ACAUCAAGGAAGAUGGCAUUUCUAG SEQID GUUUCCUUAGUAACCACAGGUUGUG NO11 NO48 SEQID CAUCAAGGAAGAUGGCAUUUCUAGU SEQID UUUCCUUAGUAACCACAGGUUGUGU NO12 NO49 SEQID AUCAAGGAAGAUGGCAUUUCUAGUU SEQID UUCCUUAGUAACCACAGGUUGUGUC NO13 NO50 SEQID UCAAGGAAGAUGGCAUUUCUAGUUU SEQID UCCUUAGUAACCACAGGUUGUGUCA NO14 NO51 SEQID CAAGGAAGAUGGCAUUUCUAGUUUG SEQID CCUUAGUAACCACAGGUUGUGUCAC NO15 NO52 SEQID AAGGAAGAUGGCAUUUCUAGUUUGG SEQID CUUAGUAACCACAGGUUGUGUCACC NO16 NO53 SEQID AGGAAGAUGGCAUUUCUAGUUUGGA SEQID UUAGUAACCACAGGUUGUGUCACCA NO17 NO54 SEQID GGAAGAUGGCAUUUCUAGUUUGGAG SEQID UAGUAACCACAGGUUGUGUCACCAG NO18 NO55 SEQID GAAGAUGGCAUUUCUAGUUUGGAGA SEQID AGUAACCACAGGUUGUGUCACCAGA NO19 NO56 SEQID AAGAUGGCAUUUCUAGUUUGGAGAU SEQID GUAACCACAGGUUGUGUCACCAGAG NO20 NO57 SEQID AGAUGGCAUUUCUAGUUUGGAGAUG SEQID UAACCACAGGUUGUGUCACCAGAGU NO21 NO58 SEQID GAUGGCAUUUCUAGUUUGGAGAUGG SEQID AACCACAGGUUGUGUCACCAGAGUA NO22 NO59 SEQID AUGGCAUUUCUAGUUUGGAGAUGGC SEQID ACCACAGGUUGUGUCACCAGAGUAA NO23 NO60 SEQID UGGCAUUUCUAGUUUGGAGAUGGCA SEQID CCACAGGUUGUGUCACCAGAGUAAC NO24 NO61 SEQID GGCAUUUCUAGUUUGGAGAUGGCAG SEQID CACAGGUUGUGUCACCAGAGUAACA NO25 NO62 SEQID GCAUUUCUAGUUUGGAGAUGGCAGU SEQID ACAGGUUGUGUCACCAGAGUAACAG NO26 NO63 SEQID CAUUUCUAGUUUGGAGAUGGCAGUU SEQID CAGGUUGUGUCACCAGAGUAACAGU NO27 NO64 SEQID AUUUCUAGUUUGGAGAUGGCAGUUU SEQID AGGUUGUGUCACCAGAGUAACAGUC NO28 NO65 SEQID UUUCUAGUUUGGAGAUGGCAGUUUC SEQID GGUUGUGUCACCAGAGUAACAGUCU NO29 NO66 SEQID UUCUAGUUUGGAGAUGGCAGUUUCC SEQID GUUGUGUCACCAGAGUAACAGUCUG NO30 NO67 SEQID UCUAGUUUGGAGAUGGCAGUUUCCU SEQID UUGUGUCACCAGAGUAACAGUCUGA NO31 NO68 SEQID CUAGUUUGGAGAUGGCAGUUUCCUU SEQID UGUGUCACCAGAGUAACAGUCUGAG NO32 NO69 SEQID UAGUUUGGAGAUGGCAGUUUCCUUA SEQID GUGUCACCAGAGUAACAGUCUGAGU NO33 NO70 SEQID AGUUUGGAGAUGGCAGUUUCCUUAG SEQID UGUCACCAGAGUAACAGUCUGAGUA NO34 NO71 SEQID GUUUGGAGAUGGCAGUUUCCUUAGU SEQID GUCACCAGAGUAACAGUCUGAGUAG NO35 NO72 SEQID UUUGGAGAUGGCAGUUUCCUUAGUA SEQID UCACCAGAGUAACAGUCUGAGUAGG NO36 NO73 SEQID UUGGAGAUGGCAGUUUCCUUAGUAA SEQID CACCAGAGUAACAGUCUGAGUAGGA NO37 NO74 SEQID UGGAGAUGGCAGUUUCCUUAGUAAC SEQID ACCAGAGUAACAGUCUGAGUAGGAG NO38 NO75 SEQID UCAAGGAAGAUGGCAUUUCU SEQID UCAAGGAAGAUGGCAUIUCU NO539 NO548 SEQID UCAAIGAAGAUGGCAUUUCU SEQID UCAAGGAAGAUGGCAUUICU NO540 NO549 SEQID UCAAGIAAGAUGGCAUUUCU SEQID UCAAGGAAGAUGGCAUUUCI NO541 NO550 SEQID UCAAGGAAIAUGGCAUUUCU SEQID UCIAGGAAGAUGGCAUUUCU NO542 NO551 SEQID UCAAGGAAGAUIGCAUUUCU SEQID UCAIGGAAGAUGGCAUUUCU NO543 NO552 SEQID UCAAGGAAGAUGICAUUUCU SEQID UCAAGGIAGAUGGCAUUUCU NO544 NO553 SEQID ICAAGGAAGAUGGCAUUUCU SEQID UCAAGGAIGAUGGCAUUUCU NO545 NO554 SEQID UCAAGGAAGAIGGCAUUUCU SEQID UCAAGGAAGIUGGCAUUUCU NO546 NO555 SEQID UCAAGGAAGAUGGCAIUUCU SEQID UCAAGGAAGAUGGCIUUUCU NO547 NO556 DMDGeneExon45 SEQID UUUGCCGCUGCCCAAUGCCAUCCUG SEQID GUUGCAUUCAAUGUUCUGACAACAG NO76 NO109 PS220 SEQID AUUCAAUGUUCUGACAACAGUUUGC SEQID UUGCAUUCAAUGUUCUGACAACAGU NO77 NO110 SEQID CCAGUUGCAUUCAAUGUUCUGACAA SEQID UGCAUUCAAUGUUCUGACAACAGUU NO78 NO111 SEQID CAGUUGCAUUCAAUGUUCUGAC SEQID GCAUUCAAUGUUCUGACAACAGUUU NO79 NO112 SEQID AGUUGCAUUCAAUGUUCUGA SEQID CAUUCAAUGUUCUGACAACAGUUUG NO80 NO113 SEQID GAUUGCUGAAUUAUUUCUUCC SEQID AUUCAAUGUUCUGACAACAGUUUGC NO81 NO114 SEQID GAUUGCUGAAUUAUUUCUUCCCCAG SEQID UCAAUGUUCUGACAACAGUUUGCCG NO82 NO115 SEQID AUUGCUGAAUUAUUUCUUCCCCAGU SEQID CAAUGUUCUGACAACAGUUUGCCCC NO83 NO116 SEQID UUGCUGAAUUAUUUCUUCCCCAGUU SEQID AAUGUUCUGACAACAGUUUGCCGCU NO84 NO117 SEQID UGCUGAAUUAUUUCUUCCCCAGUUG SEQID AUGUUCUGACAACAGUUUGCCGCUG NO85 NO118 SEQID GCUGAAUUAUUUCUUCCCCAGUUGC SEQID UGUUCUGACAACAGUUUGCCGCUGC NO86 NO119 SEQID CUGAAUUAUUUCUUCCCCAGUUGCA SEQID GUUCUGACAACAGUUUGCCGCUGCC NO87 NO120 SEQID UGAAUUAUUUCUUCCCCAGUUGCAU SEQID UUCUGACAACAGUUUGCCGCUGCCC NO88 NO121 SEQID GAAUUAUUUCUUCCCCAGUUGCAUU SEQID UCUGACAACAGUUUGCCGCUGCCCA NO89 NO122 SEQID AAUUAUUUCUUCCCCAGUUGCAUUC SEQID CUGACAACAGUUUGCCGCUGCCCAA NO90 NO123 SEQID AUUAUUUCUUCCCCAGUUGCAUUCA SEQID UGACAACAGUUUGCCGCUGCCCAAU NO91 NO124 SEQID UUAUUUCUUCCCCAGUUGCAUUCAA SEQID GACAACAGUUUGCCGCUGCCCAAUG NO92 NO125 SEQID UAUUUCUUCCCCAGUUGCAUUCAAU SEQID ACAACAGUUUGCCGCUGCCCAAUGC NO93 NO126 SEQID AUUUCUUCCCCAGUUGCAUUCAAUG SEQID CAACAGUUUGCCGCUGCCCAAUGCC NO94 NO127 SEQID UUUCUUCCCCAGUUGCAUUCAAUGU SEQID AACAGUUUGCCGCUGCCCAAUGCCA NO95 NO128 SEQID UUCUUCCCCAGUUGCAUUCAAUGUU SEQID ACAGUUUGCCGCUGCCCAAUGCCAU NO96 NO129 SEQID UCUUCCCCAGUUGCAUUCAAUGUUC SEQID CAGUUUGCCGCUGCCCAAUGCCAUC NO97 NO130 SEQID CUUCCCCAGUUGCAUUCAAUGUUCU SEQID AGUUUGCCGCUGCCCAAUGCCAUCC NO98 NO131 SEQID UUCCCCAGUUGCAUUCAAUGUUCUG SEQID GUUUGCCGCUGCCCAAUGCCAUCCU NO99 NO132 SEQID UCCCCAGUUGCAUUCAAUGUUCUGA SEQID UUUGCCGCUGCCCAAUGCCAUCCUG NO100 NO133 SEQID CCCCAGUUGCAUUCAAUGUUCUGAC SEQID UUGCCGCUGCCCAAUGCCAUCCUGG NO101 NO134 SEQID CCCAGUUGCAUUCAAUGUUCUGACA SEQID UGCCGCUGCCCAAUGCCAUCCUGGA NO102 NO135 SEQID CCAGUUGCAUUCAAUGUUCUGACAA SEQID GCCGCUGCCCAAUGCCAUCCUGGAG NO103 NO136 SEQID CAGUUGCAUUCAAUGUUCUGACAAC SEQID CCGCUGCCCAAUGCCAUCCUGGAGU NO104 NO137 SEQID AGUUGCAUUCAAUGUUCUGACAACA SEQID CGCUGCCCAAUGCCAUCCUGGAGUU NO105 NO138 SEQID UCCUGUAGAAUACUGGCAUC SEQID UGUUUUUGAGGAUUGCUGAA NO106 NO139 SEQID UGCAGACCUCCUGCCACCGCAGAUU SEQID UGUUCUGACAACAGUUUGCCGCUGCC NO107 CA NO140 CAAUGCCAUCCUGG SEQID UUGCAGACCUCCUGCCACCGCAGAU SEQID UUUGCCICUGCCCAAUGCCAUCCUG NO108 UCAGGCUUC NO557 PS305 SEQID UUUGCCGCUICCCAAUGCCAUCCUG SEQID UUUGCCGCUGCCCAIUGCCAUCCUG NO558 NO566 SEQID UUUGCCGCUGCCCAAUICCAUCCUG SEQID UUUGCCGCUGCCCAAUGCCIUCCUG NO559 NO567 SEQID UUUICCGCUGCCCAAUGCCAUCCUG SEQID UUUICCICUGCCCAAUGCCAUCCUG NO560 NO568 SEQID UUUGCCGCUGCCCAAUGCCAUCCUI SEQID UUUGCCGCUGCCCAAIGCCAUCCUG NO561 NO569 SEQID IUUGCCGCUGCCCAAUGCCAUCCUG SEQID UUUGCCGCUGCCCAAUGCCAICCUG NO562 NO570 SEQID UIUGCCGCUGCCCAAUGCCAUCCUG SEQID UUUGCCGCUGCCCAAUGCCAUCCIG NO563 NO571 SEQID UUIGCCGCUGCCCAAUGCCAUCCUG SEQID UUUGCCGCUGCCCIAUGCCAUCCUG NO564 NO572 SEQID UUUGCCGCIGCCCAAUGCCAUCCUG NO565 DMDGeneExon53 SEQID CUCUGGCCUGUCCUAAGACCUGCUC SEQID CAGCUUCUUCCUUAGCUUCCAGCCA NO141 NO165 SEQID UCUGGCCUGUCCUAAGACCUGCUCA SEQID AGCUUCUUCCUUAGCUUCCAGCCAU NO142 NO166 SEQID CUGGCCUGUCCUAAGACCUGCUCAG SEQID GCUUCUUCCUUAGCUUCCAGCCAUU NO143 NO167 SEQID UGGCCUGUCCUAAGACCUGCUCAGC SEQID CUUCUUCCUUAGCUUCCAGCCAUUG NO144 NO168 SEQID GGCCUGUCCUAAGACCUGCUCAGCU SEQID UUCUUCCUUAGCUUCCAGCCAUUGU NO145 NO169 SEQID GCCUGUCCUAAGACCUGCUCAGCUU SEQID UCUUCCUUAGCUUCCAGCCAUUGUG NO146 NO170 SEQID CCUGUCCUAAGACCUGCUCAGCUUC SEQID CUUCCUUAGCUUCCAGCCAUUGUGU NO147 NO171 SEQID CUGUCCUAAGACCUGCUCAGCUUCU SEQID UUCCUUAGCUUCCAGCCAUUGUGUU NO148 NO172 SEQID UGUCCUAAGACCUGCUCAGCUUCUU SEQID UCCUUAGCUUCCAGCCAUUGUGUUG NO149 NO173 SEQID GUCCUAAGACCUGCUCAGCUUCUUC SEQID CCUUAGCUUCCAGCCAUUGUGUUGA NO150 NO174 SEQID UCCUAAGACCUGCUCAGCUUCUUCC SEQID CUUAGCUUCCAGCCAUUGUGUUGAA NO151 NO175 SEQID CCUAAGACCUGCUCAGCUUCUUCCU SEQID UUAGCUUCCAGCCAUUGUGUUGAAU NO152 NO176 SEQID CUAAGACCUGCUCAGCUUCUUCCUU SEQID UAGCUUCCAGCCAUUGUGUUGAAUC NO153 NO177 SEQID UAAGACCUGCUCAGCUUCUUCCUUA SEQID AGCUUCCAGCCAUUGUGUUGAAUCC NO154 NO178 SEQID AAGACCUGCUCAGCUUCUUCCUUAG SEQID GCUUCCAGCCAUUGUGUUGAAUCCU NO155 NO179 SEQID AGACCUGCUCAGCUUCUUCCUUAGC SEQID CUUCCAGCCAUUGUGUUGAAUCCUU NO156 NO180 SEQID GACCUGCUCAGCUUCUUCCUUAGCU SEQID UUCCAGCCAUUGUGUUGAAUCCUUU NO157 NO181 SEQID ACCUGCUCAGCUUCUUCCUUAGCUU SEQID UCCAGCCAUUGUGUUGAAUCCUUUA NO158 NO182 SEQID CCUGCUCAGCUUCUUCCUUAGCUUC SEQID CCAGCCAUUGUGUUGAAUCCUUUAA NO159 NO183 SEQID CUGCUCAGCUUCUUCCUUAGCUUCC SEQID CAGCCAUUGUGUUGAAUCCUUUAAC NO160 NO184 SEQID UGCUCAGCUUCUUCCUUAGCUUCCA SEQID AGCCAUUGUGUUGAAUCCUUUAACA NO161 NO185 SEQID GCUCAGCUUCUUCCUUAGCUUCCAG SEQID GCCAUUGUGUUGAAUCCUUUAACAU NO162 NO186 SEQID CUCAGCUUCUUCCUUAGCUUCCAGC SEQID CCAUUGUGUUGAAUCCUUUAACAUU NO163 NO187 SEQID UCAGCUUCUUCCUUAGCUUCCAGCC SEQID CAUUGUGUUGAAUCCUUUAACAUUU NO164 NO188 DMDGeneExon44 SEQID UCAGCUUCUGUUAGCCACUG SEQID AGCUUCUGUUAGCCACUGAUUAAA NO189 NO214 SEQID UUCAGCUUCUGUUAGCCACU SEQID CAGCUUCUGUUAGCCACUGAUUAA NO190 NO215 A SEQID UUCAGCUUCUGUUAGCCACUG SEQID AGCUUCUGUUAGCCACUGAUUAAA NO191 NO216 SEQID UCAGCUUCUGUUAGCCACUGA SEQID AGCUUCUGUUAGCCACUGAU NO192 NO217 SEQID UUCAGCUUCUGUUAGCCACUGA SEQID GCUUCUGUUAGCCACUGAUU NO193 NO218 SEQID UCAGCUUCUGUUAGCCACUGA SEQID AGCUUCUGUUAGCCACUGAUU NO194 NO219 SEQID UUCAGCUUCUGUUAGCCACUGA SEQID GCUUCUGUUAGCCACUGAUUA NO195 NO220 SEQID UCAGCUUCUGUUAGCCACUGAU SEQID AGCUUCUGUUAGCCACUGAUUA NO196 NO221 SEQID UUCAGCUUCUGUUAGCCACUGAU SEQID GCUUCUGUUAGCCACUGAUUAA NO197 NO222 SEQID UCAGCUUCUGUUAGCCACUGAUU SEQID AGCUUCUGUUAGCCACUGAUUAA NO198 NO223 SEQID UUCAGCUUCUGUUAGCCACUGAUU SEQID GCUUCUGUUAGCCACUGAUUAAA NO199 NO224 SEQID UCAGCUUCUGUUAGCCACUGAUUA SEQID AGCUUCUGUUAGCCACUGAUUAAA NO200 NO225 SEQID UUCAGCUUCUGUUAGCCACUGAUA SEQID GCUUCUGUUAGCCACUGAUUAAA NO201 NO226 SEQID UCAGCUUCUGUUAGCCACUGAUUAA SEQID CCAUUUGUAUUUAGCAUGUUCCC NO202 NO227 SEQID UUCAGCUUCUGUUAGCCACUGAUUAA SEQID AGAUACCAUUUGUAUUUAGC NO203 NO228 SEQID UCAGCUUCUGUUAGCCACUGAUUAAA SEQID GCCAUUUCUCAACAGAUCU NO204 NO229 SEQID UUCAGCUUCUGUUAGCCACUGAUUAAA SEQID GCCAUUUCUCAACAGAUCUGUCA NO205 NO230 SEQID CAGCUUCUGUUAGCCACUG SEQID AUUCUCAGGAAUUUGUGUCUUUC NO206 NO231 SEQID CAGCUUCUGUUAGCCACUGAU SEQID UCUCAGGAAUUUGUGUCUUUC NO207 NO232 SEQID AGCUUCUGUUAGCCACUGAUU SEQID GUUCAGCUUCUGUUAGCC NO208 NO233 SEQID CAGCUUCUGUUAGCCACUGAUU SEQID CUGAUUAAAUAUCUUUAUAUC NO209 NO234 SEQID AGCUUCUGUUAGCCACUGAUUA SEQID GCCGCCAUUUCUCAACAG NO210 NO235 SEQID CAGCUUCUGUUAGCCACUGAUUA SEQID GUAUUUAGCAUGUUCCCA NO211 NO236 SEQID AGCUUCUGUUAGCCACUGAUUAA SEQID CAGGAAUUUGUGUCUUUC NO212 NO237 SEQID CAGCUUCUGUUAGCCACUGAUUAA SEQID UCAICUUCUGUUAGCCACUG NO213 NO575 SEQID UCAGCUUCUIUUAGCCACUG SEQID UCAGCUUCUGUUAGCCACUI NO573 NO576 SEQID UCAGCUUCUGUUAICCACUG NO574 DMDGeneExon46 SEQID GCUUUUCUUUUAGUUGCUGCUCUUU SEQID CCAGGUUCAAGUGGGAUACUAGCAA NO238 NO265 SEQID CUUUUCUUUUAGUUGCUGCUCUUUU SEQID CAGGUUCAAGUGGGAUACUAGCAAU NO239 NO266 SEQID UUUUCUUUUAGUUGCUGCUCUUUUC SEQID AGGUUCAAGUGGGAUACUAGCAAUG NO240 NO267 SEQID UUUCUUUUAGUUGCUGCUCUUUUCC SEQID GGUUCAAGUGGGAUACUAGCAAUGU NO241 NO268 SEQID UUCUUUUAGUUGCUGCUCUUUUCCA SEQID GUUCAAGUGGGAUACUAGCAAUGUU NO242 NO269 SEQID UCUUUUAGUUGCUGCUCUUUUCCAG SEQID UUCAAGUGGGAUACUAGCAAUGUUA NO243 NO270 SEQID CUUUUAGUUGCUGCUCUUUUCCAGG SEQID UCAACUGGGAUACUAGCAAUGUUAU NO244 NO271 SEQID UUUUAGUUGCUGCUCUUUUCCAGGU SEQID CAAGUGGGAUACUAGCAAUGUUAUC NO245 NO272 SEQID UUUAGUUGCUGCUCUUUUCCAGGUU SEQID AAGUGGGAUACUAGCAAUGUUAUCU NO246 NO273 SEQID UUAGUUGCUGCUCUUUUCCAGGUUC SEQID AGUGGGAUACUAGCAAUGUUAUCUG NO247 NO274 SEQID UAGUUGCUGCUCUUUUCCAGGUUCA SEQID GUGGGAUACUAGCAAUGUUAUCUGC NO248 NO275 SEQID AGUUGCUGCUCUUUUCCAGGUUCAA SEQID UGGGAUACUAGCAAUGUUAUCUGCU NO249 NO276 SEQID GUUGCUGCUCUUUUCCAGGUUCAAG SEQID GGGAUACUAGCAAUGUUAUCUGCUU NO250 NO277 SEQID UUGCUGCUCUUUUCCAGGUUCAAGU SEQID GGAUACUAGCAAUGUUAUCUGCUUC NO251 NO278 SEQID UGCUGCUCUUUUCCAGGUUCAAGUG SEQID GAUACUAGCAAUGUUAUCUGCUUCC NO252 NO279 SEQID GCUGCUCUUUUCCAGGUUCAAGUGG SEQID AUACUAGCAAUGUUAUCUGCUUCCU NO253 NO280 SEQID CUGCUCUUUUCCAGGUUCAAGUGGG SEQID UACUAGCAAUGUUAUCUGCUUCCUC NO254 NO281 SEQID UGCUCUUUUCCAGGUUCAAGUGGGA SEQID ACUAGCAAUGUUAUCUGCUUCCUCC NO255 NO282 SEQID GCUCUUUUCCAGGUUCAAGUGGGAC SEQID CUAGCAAUGUUAUCUGCUUCCUCCA NO256 NO283 SEQID CUCUUUUCCAGGUUCAAGUGGGAUA SEQID UAGCAAUGUUAUCUGCUUCCUCCAA NO257 NO284 SEQID UCUUUUCCAGGUUCAAGUGGGAUAC SEQID AGCAAUGUUAUCUGCUUCCUCCAAC NO258 NO285 SEQID UCUUUUCCAGGUUCAAGUGG SEQID GCAAUGUUAUCUGCUUCCUCCAACC NO259 NO286 SEQID CUUUUCCAGGUUCAAGUGGGAUACU SEQID CAAUGUUAUCUGCUUCCUCCAACCA NO260 NO287 SEQID UUUUCCAGGUUCAAGUGGGAUACUA SEQID AAUGUUAUCUGCUUCCUCCAACCAU NO261 NO288 SEQID UUUCCAGGUUCAAGUGGGAUACUAG SEQID AUGUUAUCUGCUUCCUCCAACCAUA NO262 NO289 SEQID UUCCAGGUUCAAGUGGGAUACUAGC SEQID UGUUAUCUGCUUCCUCCAACCAUAA NO263 NO290 SEQID UCCAGGUUCAAGUGGGAUACUAGCA NO264 DMDGeneExon52 SEQID AGCCUCUUGAUUGCUGGUCUUGUUU SEQID UUGGGCAGCGGUAAUGAGUUCUUCC NO291 NO326 SEQID GCCUCUUGAUUGCUGGUCUUGUUUU SEQID UGGGCAGCGGUAAUGAGUUCUUCCA NO292 NO327 SEQID CCUCUUGAUUGCUGGUCUUGUUUUU SEQID GGGCAGCGGUAAUGAGUUCUUCCAA NO293 NO328 SEQID CCUCUUGAUUGCUGGUCUUG SEQID GGCAGCGGUAAUGAGUUCUUCCAAC NO294 NO329 SEQID CUCUUGAUUGCUGGUCUUGUUUUUC SEQID GCAGCGGUAAUGAGUUCUUCCAACU NO295 NO330 SEQID UCUUGAUUGCUGGUCUUGUUUUUCA SEQID CAGCGGUAAUGAGUUCUUCCAACUG NO296 NO331 SEQID CUUGAUUGCUGGUCUUGUUUUUCAA SEQID AGCGGUAAUGAGUUCUUCCAACUGG NO297 NO332 SEQID UUGAUUGCUGGUCUUGUUUUUCAAA SEQID GCGGUAAUGAGUUCUUCCAACUGGG NO298 NO333 SEQID UGAUUGCUGGUCUUGUUUUUCAAAU SEQID CGGUAAUGAGUUCUUCCAACUGGGG NO299 NO334 SEQID GAUUGCUGGUCUUGUUUUUCAAAUU SEQID GGUAAUGAGUUCUUCCAACUGGGGA NO300 NO335 SEQID GAUUGCUGGUCUUGUUUUUC SEQID GGUAAUGAGUUCUUCCAACUGG NO301 NO336 SEQID AUUGCUGGUCUUGUUUUUCAAAUUU SEQID GUAAUGAGUUCUUCCAACUGGGGAC NO302 NO337 SEQID UUGCUGGUCUUGUUUUUCAAAUUUU SEQID UAAUGAGUUCUUCCAACUGGGGACG NO303 NO338 SEQID UGCUGGUCUUGUUUUUCAAAUUUUG SEQID AAUGAGUUCUUCCAACUGGGGACGC NO304 NO339 SEQID GCUGGUCUUGUUUUUCAAAUUUUGG SEQID AUGAGUUCUUCCAACUGGGGACGCC NO305 NO340 SEQID CUGGUCUUGUUUUUCAAAUUUUGGG SEQID UGAGUUCUUCCAACUGGGGACGCCU NO306 NO341 SEQID UGGUCUUGUUUUUCAAAUUUUGGGC SEQID GAGUUCUUCCAACUGGGGACGCCUC NO307 NO342 SEQID GGUCUUGUUUUUCAAAUUUUGGGCA SEQID AGUUCUUCCAACUGGGGACGCCUCU NO308 NO343 SEQID GUCUUGUUUUUCAAAUUUUGGGCAG SEQID GUUCUUCCAACUGGGGACGCCUCUG NO309 NO344 SEQID UCUUGUUUUUCAAAUUUUGGGCAGC SEQID UUCUUCCAACUGGGGACGCCUCUGU NO310 NO345 SEQID CUUGUUUUUCAAAUUUUGGGCAGCG SEQID UCUUCCAACUGGGGACGCCUCUGUU NO311 NO346 SEQID UUGUUUUUCAAAUUUUGGGCAGCGG SEQID CUUCCAACUGGGGACGCCUCUGUUC NO312 NO347 SEQID UGUUUUUCAAAUUUUGGGCAGCGGU SEQID UUCCAACUGGGGACGCCUCUGUUCC NO313 NO348 SEQID GUUUUUCAAAUUUUGGGCAGCGGUA SEQID UCCAACUGGGGACGCCUCUGUUCCA NO314 NO349 SEQID UUUUUCAAAUUUUGGGCAGCGGUAA SEQID CCAACUGGGGACGCCUCUGUUCCAA NO315 NO350 SEQID UUUUCAAAUUUUGGGCAGCGGUAAU SEQID CAACUGGGGACGCCUCUGUUCCAAA NO316 NO351 SEQID UUUCAAAUUUUGGGCAGCGGUAAUG SEQID AACUGGGGACGCCUCUGUUCCAAAU NO317 NO352 SEQID UUCAAAUUUUGGGCAGCGGUAAUGA SEQID ACUGGGGACGCCUCUGUUCCAAAUC NO318 NO353 SEQID UCAAAUUUUGGGCAGCGGUAAUGAG SEQID CUGGGGACGCCUCUGUUCCAAAUCC NO319 NO354 SEQID CAAAUUUUGGGCAGCGGUAAUGAGU SEQID UGGGGACGCCUCUGUUCCAAAUCCU NO320 NO355 SEQID AAAUUUUGGGCAGCGGUAAUGAGUU SEQID GGGGACGCCUCUGUUCCAAAUCCUG NO321 NO356 SEQID AAUUUUGGGCAGCGGUAAUGAGUUC SEQID GGGACGCCUCUGUUCCAAAUCCUGC NO322 NO357 SEQID AUUUUGGGCAGCGGUAAUGAGUUCU SEQID GGACGCCUCUGUUCCAAAUCCUGCA NO323 NO358 SEQID UUUUGGGCAGCGGUAAUGAGUUCUU SEQID GACGCCUCUGUUCCAAAUCCUGCAU NO324 NO359 SEQID UUUGGGCAGCGGUAAUGAGUUCUUC NO325 DMDGeneExon50 SEQID CCAAUAGUGGUCAGUCCAGGAGCUA SEQID CUAGGUCAGGCUGCUUUGCCCUCAG NO360 NO386 SEQID CAAUAGUGGUCAGUCCAGGAGCUAG SEQID UAGGUCAGGCUGCUUUGCCCUCAGC NO361 NO387 SEQID AAUAGUGGUCAGUCCAGGAGCUAGG SEQID AGGUCAGGCUGCUUUGCCCUCAGCU NO362 NO388 SEQID AUAGUGGUCAGUCCAGGAGCUAGGU SEQID GGUCAGGCUGCUUUGCCCUCAGCUC NO363 NO389 SEQID AUAGUGGUCAGUCCAGGAGCU SEQID GUCAGGCUGCUUUGCCCUCAGCUCU NO364 NO390 SEQID UAGUGGUCAGUCCAGGAGCUAGGUC SEQID UCAGGCUGCUUUGCCCUCAGCUCUU NO365 NO391 SEQID AGUGGUCAGUCCAGGAGCUAGGUCA SEQID CAGGCUGCUUUGCCCUCAGCUCUUG NO366 NO392 SEQID GUGGUCAGUCCAGGAGCUAGGUCAG SEQID AGGCUGCUUUGCCCUCAGCUCUUGA NO367 NO393 SEQID UGGUCAGUCCAGGAGCUAGGUCAGG SEQID GGCUGCUUUGCCCUCAGCUCUUGAA NO368 NO394 SEQID GGUCAGUCCAGGAGCUAGGUCAGGC SEQID GCUGCUUUGCCCUCAGCUCUUGAAG NO369 NO395 SEQID GUCAGUCCAGGAGCUAGGUCAGGCU SEQID CUGCUUUGCCCUCAGCUCUUGAAGU NO370 NO396 SEQID UCAGUCCAGGAGCUAGGUCAGGCUG SEQID UGCUUUGCCCUCAGCUCUUGAAGUA NO371 NO397 SEQID CAGUCCAGGAGCUAGGUCAGGCUGC SEQID GCUUUGCCCUCAGCUCUUGAAGUAA NO372 NO398 SEQID AGUCCAGGAGCUAGGUCAGGCUGCU SEQID CUUUGCCCUCAGCUCUUGAAGUAAA NO373 NO399 SEQID GUCCAGGAGCUAGGUCAGGCUGCUU SEQID UUUGCCCUCAGCUCUUGAAGUAAAC NO374 NO400 SEQID UCCAGGAGCUAGGUCAGGCUGCUUU SEQID UUGCCCUCAGCUCUUGAAGUAAACG NO375 NO401 SEQID CCAGGAGCUAGGUCAGGCUGCUUUG SEQID UGCCCUCAGCUCUUGAAGUAAACGG NO376 NO402 SEQID CAGGAGCUAGGUCAGGCUGCUUUGC SEQID GCCCUCAGCUCUUGAAGUAAACGGU NO377 NO403 SEQID AGGAGCUAGGUCAGGCUGCUUUGCC SEQID CCCUCAGCUCUUGAAGUAAACGGUU NO378 NO404 SEQID GGAGCUAGGUCAGGCUGCUUUGCCC SEQID CCUCAGCUCUUGAAGUAAAC NO379 NO405 SEQID GAGCUAGGUCAGGCUGCUUUGCCCU SEQID CCUCAGCUCUUGAAGUAAACG NO380 NO406 SEQID AGCUAGGUCAGGCUGCUUUGCCCUC SEQID CUCAGCUCUUGAAGUAAACG NO381 NO407 SEQID GCUAGGUCAGGCUGCUUUGCCCUCA SEQID CCUCAGCUCUUGAAGUAAACGGUUU NO382 NO408 SEQID CUCAGCUCUUGAAGUAAACGGUUUA SEQID UCAGCUCUUGAAGUAAACGGUUUAC NO383 NO409 SEQID CAGCUCUUGAAGUAAACGGUUUACC SEQID AGCUCUUGAAGUAAACGGUUUACCG NO384 NO410 SEQID GCUCUUGAAGUAAACGGUUUACCGC SEQID CUCUUGAAGUAAACGGUUUACCGCC NO385 NO411 DMDGeneExon43 SEQID CCACAGGCGUUGCACUUUGCAAUGC SEQID UCUUCUUGCUAUGAAUAAUGUCAAU NO412 NO443 SEQID CACAGGCGUUGCACUUUGCAAUGCU SEQID CUUCUUGCUAUGAAUAAUGUCAAUC NO413 NO444 SEQID ACAGGCGUUGCACUUUGCAAUGCUG SEQID UUCUUGCUAUGAAUAAUGUCAAUCC NO414 NO445 SEQID CAGGCGUUGCACUUUGCAAUGCUGC SEQID UCUUGCUAUGAAUAAUGUCAAUCCG NO415 NO446 SEQID AGGCGUUGCACUUUGCAAUGCUGCU SEQID CUUGCUAUGAAUAAUGUCAAUCCGA NO416 NO447 SEQID GGCGUUGCACUUUGCAAUGCUGCUG SEQID UUGCUAUGAAUAAUGUCAAUCCGAC NO417 NO448 SEQID GCGUUGCACUUUGCAAUGCUGCUGU SEQID UGCUAUGAAUAAUGUCAAUCCGACC NO418 NO449 SEQID CGUUGCACUUUGCAAUGCUGCUGUC SEQID GCUAUGAAUAAUGUCAAUCCGACCU NO419 NO450 SEQID CGUUGCACUUUGCAAUGCUGCUG SEQID CUAUGAAUAAUGUCAAUCCGACCUG NO420 NO451 SEQID GUUGCACUUUGCAAUGCUGCUGUCU SEQID UAUGAAUAAUGUCAAUCCGACCUGA NO421 NO452 SEQID UUGCACUUUGCAAUGCUGCUGUCUU SEQID AUGAAUAAUGUCAAUCCGACCUGAG NO422 NO453 SEQID UGCACUUUGCAAUGCUGCUGUCUUC SEQID UGAAUAAUGUCAAUCCGACCUGAGC NO423 NO454 SEQID GCACUUUGCAAUGCUGCUGUCUUCU SEQID GAAUAAUGUCAAUCCGACCUGAGCU NO424 NO455 SEQID CACUUUGCAAUGCUGCUGUCUUCUU SEQID AAUAAUGUCAAUCCGACCUGAGCUU NO425 NO456 SEQID ACUUUGCAAUGCUGCUGUCUUCUUG SEQID AUAAUGUCAAUCCGACCUGAGCUUU NO426 NO457 SEQID CUUUGCAAUGCUGCUGUCUUCUUGC SEQID UAAUGUCAAUCCGACCUGAGCUUUG NO427 NO458 SEQID UUUGCAAUGCUGCUGUCUUCUUGCU SEQID AAUGUCAAUCCGACCUGAGCUUUGU NO428 NO459 SEQID UUGCAAUGCUGCUGUCUUCUUGCUA SEQID AUGUCAAUCCGACCUGAGCUUUGUU NO429 NO460 SEQID UGCAAUGCUGCUGUCUUCUUGCUAU SEQID UGUCAAUCCGACCUGAGCUUUGUUG NO430 NO461 SEQID GCAAUGCUGCUGUCUUCUUGCUAUG SEQID GUCAAUCCGACCUGAGCUUUGUUGU NO431 NO462 SEQID CAAUGCUGCUGUCUUCUUGCUAUGA SEQID UCAAUCCGACCUGAGCUUUGUUGUA NO432 NO463 SEQID AAUGCUGCUGUCUUCUUGCUAUGAA SEQID CAAUCCGACCUGAGCUUUGUUGUAG NO433 NO464 SEQID AUGCUGCUGUCUUCUUGCUAUGAAU SEQID AAUCCGACCUGAGCUUUGUUGUAGA NO434 NO465 SEQID UGCUGCUGUCUUCUUGCUAUGAAUA SEQID AUCCGACCUGAGCUUUGUUGUAGAC NO435 NO466 SEQID GCUGCUGUCUUCUUGCUAUGAAUAA SEQID UCCGACCUGAGCUUUGUUGUAGACU NO436 NO467 SEQID CUGCUGUCUUCUUGCUAUGAAUAAU SEQID CCGACCUGAGCUUUGUUGUAGACUA NO437 NO468 SEQID UGCUGUCUUCUUGCUAUGAAUAAUG SEQID CGACCUGAGCUUUGUUGUAG NO438 NO469 SEQID GCUGUCUUCUUGCUAUGAAUAAUGU SEQID CGACCUGAGCUUUGUUGUAGACUAU NO439 NO470 SEQID CUGUCUUCUUGCUAUGAAUAAUGUC SEQID GACCUGAGCUUUGUUGUAGACUAUC NO440 NO471 SEQID UGUCUUCUUGCUAUGAAUAAUGUCA SEQID ACCUGAGCUUUGUUGUAGACUAUCA NO441 NO472 SEQID GUCUUCUUGCUAUGAAUAAUGUCAA SEQID CCUGAGCUUUGUUGUAGACUAUC NO442 NO473 DMDGeneExon6 SEQID CAUUUUUGACCUACAUGUGG SEQID AUUUUUGACCUACAUGGGAAAG NO474 NO479 SEQID UUUGACCUACAUGUGGAAAG SEQID UACGAGUUGAUUGUCGGACCCAG NO475 NO480 SEQID UACAUUUUUGACCUACAUGUGGAAA SEQID GUGGUCUCCUUACCUAUGACUGUGG NO476 G NO481 SEQID GGUCUCCUUACCUAUGA SEQID UGUCUCAGUAAUCUUCUUACCUAU NO477 NO482 SEQID UCUUACCUAUGACUAUGGAUGAGA NO478 DMDGeneExon7 SEQID UGCAUGUUCCAGUCGUUGUGUGG SEQID AUUUACCAACCUUCAGGAUCGAGUA NO483 NO485 SEQID CACUAUUCCAGUCAAAUAGGUCUGG SEQID GGCCUAAAACACAUACACAUA NO484 NO486 DMDGeneExon8 SEQID GAUAGGUGGUAUCAACAUCUGUAA SEQID UGUUGUUGUUUAUGCUCAUU NO487 NO490 SEQID GAUAGGUGGUAUCAACAUCUG SEQID GUACAUUAAGAUGGACUUC NO488 NO491 SEQID CUUCCUGGAUGGCUUGAAU NO489 DMDGeneExon55 SEQID CUGUUGCAGUAAUCUAUGAG SEQID UGCCAUUGUUUCAUCAGCUCUUU NO492 NO495 SEQID UGCAGUAAUCUAUGAGUUUC SEQID UCCUGUAGGACAUUGGCAGU NO493 NO496 SEQID GAGUCUUCUAGGAGCCUU SEQID CUUGGAGUCUUCUAGGAGCC NO494 NO497 DMDGeneExon2 SEQID CCAUUUUGUGAAUGUUUUCUUUUG SEQID GAAAAUUGUGCAUUUACCCAUUUU NO498 AACAUC NO500 SEQID CCCAUUUUGUGAAUGUUUUCUUUU SEQID UUGUGCAUUUACCCAUUUUGUG NO499 NO501 DMDGeneExon11 SEQID CCCUGAGGCAUUCCCAUCUUGAAU SEQID CUUGAAUUUAGGAGAUUCAUCUG NO502 NO504 SEQID AGGACUUACUUGCUUUGUUU SEQID CAUCUUCUGAUAAUUUUCCUGUU NO503 NO505 DMDGeneExon17 SEQID CCAUUACAGUUGUCUGUGUU SEQID UAAUCUGCCUCUUCUUUUGG NO506 NO508 SEQID UGACAGCCUGUGAAAUCUGUGAG NO507 DMDGeneExon19 SEQID CAGCAGUAGUUGUCAUCUGC SEQID GCCUGAGCUGAUCUGCUGGCAUCUUG NO509 NO511 CAGUU SEQID GCCUGAGCUGAUCUGCUGGCAUCUU SEQID UCUGCUGGCAUCUUGC NO510 GC NO512 DMDGeneExon21 SEQID GCCGGUUGACUUCAUCCUGUGC SEQID CUGCAUCCAGGAACAUGGGUCC NO513 NO516 SEQID GUCUGCAUCCAGGAACAUGGGUC SEQID GUUGAAGAUCUGAUAGCCGGUUGA NO514 NO517 SEQID UACUUACUGUCUGUAGCUCUUUCU NO515 DMDGeneExon57 SEQID UAGGUGCCUGCCGGCUU SEQID CUGAACUGCUGGAAAGUCGCC NO518 NO520 SEQID UUCAGCUGUAGCCACACC SEQID CUGGCUUCCAAAUGGGACCUGAAAAA NO519 NO521 GAAC DMDGeneExon59 SEQID CAAUUUUUCCCACUCAGUAUU SEQID UCCUCAGGAGGCAGCUCUAAAU NO522 NO524 SEQID UUGAAGUUCCUGGAGUCUU NO523 DMDGeneExon62 SEQID UGGCUCUCUCCCAGGG SEQID GGGCACUUUGUUUGGCG NO525 NO527 SEQID GAGAUGGCUCUCUCCCAGGGACCCU NO526 GG DMDGeneExon63 SEQID GGUCCCAGCAAGUUGUUUG SEQID GUAGAGCUCUGUCAUUUUGGG NO528 NO530 SEQID UGGGAUGGUCCCAGCAAGUUGUUUG NO529 DMDGeneExon65 SEQID GCUCAAGAGAUCCACUGCAAAAAAC SEQID UCUGCAGGAUAUCCAUGGGCUGGUC NO531 NO533 SEQID GCCAUACGUACGUAUCAUAAACAUU NO532 C DMDGeneExon66 SEQID GAUCCUCCCUGUUCGUCCCCUAUUA NO534 UG DMDGeneExon69 SEQID UGCUUUAGACUCCUGUACCUGAUA NO535 DMDGeneExon75 SEQID GGCGGCCUUUGUGUUGAC SEQID CCUUUAUGUUCGUGCUGCU NO536 NO538 SEQID GGACAGGCCUUUAUGUUCGUGCUGC NO537 HumanIGF-1Isoform4aminoacidsequence SEQIDNO577: MGKISSLPTQLFKCCFCDFLKVKMHTMSSSHLFYLALCLLTFTSSATAGPETLCGAELV DALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA RSVRAQRHTDMPKTQKEVHLKNASRGSAGNKNYRM