ES2714290T3 - Composiciones de salto de exón para el tratamiento de la distrofia muscular - Google Patents
Composiciones de salto de exón para el tratamiento de la distrofia muscular Download PDFInfo
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- ES2714290T3 ES2714290T3 ES14723583T ES14723583T ES2714290T3 ES 2714290 T3 ES2714290 T3 ES 2714290T3 ES 14723583 T ES14723583 T ES 14723583T ES 14723583 T ES14723583 T ES 14723583T ES 2714290 T3 ES2714290 T3 ES 2714290T3
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N15/09—Recombinant DNA-technology
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- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/11—Antisense
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3233—Morpholino-type ring
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- C12N2310/35—Nature of the modification
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- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
- C12N2310/3535—Nitrogen
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2320/00—Applications; Uses
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- C12N2320/33—Alteration of splicing
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- Neurology (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361782706P | 2013-03-14 | 2013-03-14 | |
| PCT/US2014/029766 WO2014153240A2 (en) | 2013-03-14 | 2014-03-14 | Exon skipping compositions for treating muscular dystrophy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2714290T3 true ES2714290T3 (es) | 2019-05-28 |
Family
ID=50694008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14723583T Active ES2714290T3 (es) | 2013-03-14 | 2014-03-14 | Composiciones de salto de exón para el tratamiento de la distrofia muscular |
Country Status (26)
| Country | Link |
|---|---|
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Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2206781T3 (en) | 2004-06-28 | 2016-03-07 | Univ Western Australia | The antisense oligonucleotides in inducing exon-skipping and methods of use thereof |
| ES2914775T3 (es) * | 2007-10-26 | 2022-06-16 | Academisch Ziekenhuis Leiden | Medios y métodos para contrarresta trastornos del músculo |
| IL304042A (en) | 2008-10-24 | 2023-08-01 | Sarepta Therapeutics Inc | Antisense compounds for inducing axon termination and preparations containing them for the treatment of muscular dystrophy |
| IL297299A (en) | 2009-11-12 | 2022-12-01 | Univ Western Australia | Antisense oligonucleotides for inducing exon skipping in the dystrophin gene |
| TWI541024B (zh) | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| KR20250047401A (ko) | 2013-03-14 | 2025-04-03 | 사렙타 쎄러퓨틱스 인코퍼레이티드 | 근육 이영양증의 치료를 위한 엑손 스키핑 조성물 |
| CA2906812A1 (en) | 2013-03-15 | 2014-09-18 | Sarepta Therapeutics, Inc. | Improved compositions for treating muscular dystrophy |
| FR3044926B1 (fr) * | 2015-12-09 | 2020-01-31 | Genethon | Outils de therapie genique efficaces pour le saut de l'exon 53 de la dystrophine |
| JOP20200228A1 (ar) | 2015-12-21 | 2017-06-16 | Novartis Ag | تركيبات وطرق لخفض تعبير البروتين tau |
| CA3024182A1 (en) * | 2016-05-24 | 2017-11-30 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| US10875880B2 (en) * | 2016-05-24 | 2020-12-29 | Sarepta Therapeutics, Inc. | Processes for preparing oligomers |
| MA45362A (fr) * | 2016-05-24 | 2019-04-10 | Sarepta Therapeutics Inc | Procédés de préparation d'oligomères morpholino de phosphorodiamidate |
| US11472824B2 (en) | 2016-05-24 | 2022-10-18 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| CA3024456A1 (en) | 2016-05-24 | 2017-11-30 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| CN109152775B (zh) * | 2016-06-30 | 2022-04-26 | 萨勒普塔医疗公司 | 制备磷酸二酰胺吗啉代寡聚物的方法 |
| CA3024153A1 (en) * | 2016-06-30 | 2017-11-30 | Sarepta Therapeutics, Inc. | Processes for preparing phosphorodiamidate morpholino oligomers |
| WO2018005805A1 (en) * | 2016-06-30 | 2018-01-04 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystrophy |
| EP4252845A3 (en) * | 2016-07-05 | 2024-05-22 | BioMarin Technologies B.V. | Pre-mrna splice switching or modulating oligonucleotides comprising bicyclic scaffold moieties, with improved characteristics for the treatment of genetic disorders |
| EP3485015A4 (en) * | 2016-07-15 | 2020-07-29 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS OF MODULATION OF DYSTROPHINE TRANSCRIPT |
| EP3515445A4 (en) | 2016-09-20 | 2020-05-27 | The Regents of The University of Colorado, A Body Corporate | SYNTHESIS OF BACKBONE-MODIFIED MORPHOLINO-OLIGONUCLEOTIDES AND CHIMERES WITH THE AID OF PHOSPHORAMIDITE CHEMISTRY |
| ES3051834T3 (en) * | 2016-12-19 | 2025-12-30 | Sarepta Therapeutics Inc | Exon skipping oligomer conjugates for muscular dystrophy |
| PT3554553T (pt) | 2016-12-19 | 2022-08-04 | Sarepta Therapeutics Inc | Conjugados oligoméricos de salto de exão para a distrofia muscular |
| CN117298290A (zh) | 2016-12-19 | 2023-12-29 | 萨勒普塔医疗公司 | 用于肌肉萎缩症的外显子跳跃寡聚体缀合物 |
| MX2020002038A (es) * | 2017-08-31 | 2020-09-18 | Sarepta Therapeutics Inc | Métodos para el tratamiento de distrofia muscular. |
| EA201991450A1 (ru) * | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| JP7218361B2 (ja) * | 2017-09-25 | 2023-02-06 | サレプタ セラピューティクス， インコーポレイテッド | 高速流動合成を介してホスホロジアミデートモルホリノオリゴマーを調製するための方法 |
| US20200254002A1 (en) | 2017-09-28 | 2020-08-13 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
| EP3765030A4 (en) * | 2018-03-16 | 2022-01-26 | Sarepta Therapeutics, Inc. | CHIMERIC PEPTIDES FOR ANTISENSE ADMINISTRATION |
| EP3784248A4 (en) * | 2018-04-26 | 2022-08-10 | Sarepta Therapeutics, Inc. | EXON-SKIPPING OLIGOMERS AND OLIGOMER CONJUGATES FOR MUSCULAR DYSTROPHY |
| US10758629B2 (en) | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| JP7579147B2 (ja) * | 2018-06-14 | 2024-11-07 | サレプタ セラピューティクス， インコーポレイテッド | 筋ジストロフィーに対するエクソンスキッピングオリゴマーおよびオリゴマーコンジュゲート |
| NZ770540A (en) * | 2018-06-26 | 2025-12-19 | Nippon Shinyaku Co Ltd | Composition comprising antisense oligonucleotide and use thereof for treatment of duchenne muscular dystrophy |
| US11168141B2 (en) | 2018-08-02 | 2021-11-09 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US20210308273A1 (en) | 2018-08-02 | 2021-10-07 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| JP2021533200A (ja) | 2018-08-02 | 2021-12-02 | ダイン セラピューティクス, インコーポレーテッドDyne Therapeutics, Inc. | 顔面・肩甲・上腕筋ジストロフィーを処置するための筋標的化複合体およびそれらの使用 |
| US12018087B2 (en) | 2018-08-02 | 2024-06-25 | Dyne Therapeutics, Inc. | Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject |
| GB201812972D0 (en) | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| GB201812980D0 (en) | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| BR112021010982A2 (pt) | 2018-12-07 | 2021-08-31 | Oxford University Innovation Limited | Ligantes |
| EP3954395A4 (en) * | 2019-04-08 | 2023-06-28 | National University Corporation Tokyo Medical and Dental University | Pharmaceutical composition for muscle disease treatment |
| WO2021025899A1 (en) | 2019-08-02 | 2021-02-11 | Sarepta Therapeutics, Inc. | Phosphorodiamidate morpholino oligomer pharmaceutical compositions |
| CA3153902A1 (en) | 2019-10-16 | 2021-04-22 | Pardis SABETI | Engineered muscle targeting compositions |
| WO2022006871A1 (en) * | 2020-07-10 | 2022-01-13 | Changzhou Syntheall Pharmaceuticals Co., Ltd. | Processes for preparing oligonucleotides |
| WO2022171972A1 (en) * | 2021-02-12 | 2022-08-18 | Oxford University Innovation Limited | Cell-penetrating peptide conjugates and methods of their use |
| WO2022213118A1 (en) | 2021-03-31 | 2022-10-06 | Entrada Therapeutics, Inc. | Cyclic cell penetrating peptides |
| WO2022217366A1 (en) * | 2021-04-14 | 2022-10-20 | The Royal Institution For The Advancement Of Learning/Mcgill University | Modified oligonucleotides for the treatment of duchenne muscular dystrophy |
| EP4337264A1 (en) | 2021-05-10 | 2024-03-20 | Entrada Therapeutics, Inc. | Compositions and methods for modulating tissue distribution of intracellular therapeutics |
| US11638761B2 (en) | 2021-07-09 | 2023-05-02 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy |
| MX2024000489A (es) | 2021-07-09 | 2024-04-09 | Dyne Therapeutics Inc | Complejos dirigidos al musculo y formulaciones para el tratamiento de las distrofinopatías. |
| US11969475B2 (en) | 2021-07-09 | 2024-04-30 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| US11771776B2 (en) | 2021-07-09 | 2023-10-03 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
| US20250066396A1 (en) | 2021-12-27 | 2025-02-27 | Nippon Shinyaku Co., Ltd. | Method for producing oligonucleic acid compound |
| EP4493693A1 (en) * | 2022-03-17 | 2025-01-22 | Sarepta Therapeutics, Inc. | Phosphorodiamidate morpholino oligomer conjugates |
| WO2024073588A1 (en) * | 2022-09-28 | 2024-04-04 | Board Of Regents, The University Of Texas System | Respiratory dry powder delivery |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH445129A (fr) | 1964-04-29 | 1967-10-15 | Nestle Sa | Procédé pour la préparation de composés d'inclusion à poids moléculaire élevé |
| US3459731A (en) | 1966-12-16 | 1969-08-05 | Corn Products Co | Cyclodextrin polyethers and their production |
| US3453257A (en) | 1967-02-13 | 1969-07-01 | Corn Products Co | Cyclodextrin with cationic properties |
| US3426011A (en) | 1967-02-13 | 1969-02-04 | Corn Products Co | Cyclodextrins with anionic properties |
| US3453259A (en) | 1967-03-22 | 1969-07-01 | Corn Products Co | Cyclodextrin polyol ethers and their oxidation products |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US5521063A (en) | 1985-03-15 | 1996-05-28 | Antivirals Inc. | Polynucleotide reagent containing chiral subunits and methods of use |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| AU5661386A (en) | 1985-03-15 | 1986-10-13 | Stirchak, E. | Stereoregular polynucleotide-binding polymers |
| US5217866A (en) | 1985-03-15 | 1993-06-08 | Anti-Gene Development Group | Polynucleotide assay reagent and method |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| EP0786522A2 (en) | 1992-07-17 | 1997-07-30 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecules for treatment of stenotic conditions |
| DK0698092T3 (da) | 1993-05-11 | 2007-11-26 | Univ North Carolina | Antisenseoligonukleotider, der bekæmper uregelmæssig splejsning,og fremgangsmåder til anvendelse deraf |
| US5753613A (en) | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
| US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| IL115849A0 (en) | 1994-11-03 | 1996-01-31 | Merz & Co Gmbh & Co | Tangential filtration preparation of liposomal drugs and liposome product thereof |
| WO1999042091A2 (en) | 1998-02-19 | 1999-08-26 | Massachusetts Institute Of Technology | Use of polycations as endosomolytic agents |
| US6683173B2 (en) | 1998-04-03 | 2004-01-27 | Epoch Biosciences, Inc. | Tm leveling methods |
| US6210892B1 (en) | 1998-10-07 | 2001-04-03 | Isis Pharmaceuticals, Inc. | Alteration of cellular behavior by antisense modulation of mRNA processing |
| AU2281201A (en) | 1999-12-29 | 2001-07-09 | A. James Mixson | Histidine copolymer and methods for using same |
| US7070807B2 (en) | 1999-12-29 | 2006-07-04 | Mixson A James | Branched histidine copolymers and methods for using same |
| EP1390490B1 (en) | 2001-05-24 | 2009-04-15 | Genzyme Corporation | Muscle-specific expression vectors |
| AU2003225410A1 (en) | 2003-03-21 | 2004-10-11 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
| DK2206781T3 (en) * | 2004-06-28 | 2016-03-07 | Univ Western Australia | The antisense oligonucleotides in inducing exon-skipping and methods of use thereof |
| AU2006213686A1 (en) * | 2005-02-09 | 2006-08-17 | Avi Bio Pharma, Inc. | Antisense composition and method for treating muscle atrophy |
| US8067571B2 (en) * | 2005-07-13 | 2011-11-29 | Avi Biopharma, Inc. | Antibacterial antisense oligonucleotide and method |
| KR101789603B1 (ko) | 2005-11-10 | 2017-11-21 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | Ｔｎｆ 수퍼패밀리 수용체에 대한 스플라이스 스위칭올리고머 및 염증성 질환 치료용 약제학적 조성물 |
| SI2024499T1 (en) | 2006-05-10 | 2018-04-30 | Sarepta Therapeutics, Inc. | Analogues of the oligonucleotide, with cationic links between subunits |
| US20070265215A1 (en) * | 2006-05-11 | 2007-11-15 | Iversen Patrick L | Antisense restenosis composition and method |
| US20100016215A1 (en) | 2007-06-29 | 2010-01-21 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| ES2914775T3 (es) * | 2007-10-26 | 2022-06-16 | Academisch Ziekenhuis Leiden | Medios y métodos para contrarresta trastornos del músculo |
| US8299206B2 (en) | 2007-11-15 | 2012-10-30 | Avi Biopharma, Inc. | Method of synthesis of morpholino oligomers |
| US8076476B2 (en) | 2007-11-15 | 2011-12-13 | Avi Biopharma, Inc. | Synthesis of morpholino oligomers using doubly protected guanine morpholino subunits |
| WO2009127230A1 (en) | 2008-04-16 | 2009-10-22 | Curevac Gmbh | MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION |
| US8084601B2 (en) * | 2008-09-11 | 2011-12-27 | Royal Holloway And Bedford New College Royal Holloway, University Of London | Oligomers |
| IL304042A (en) * | 2008-10-24 | 2023-08-01 | Sarepta Therapeutics Inc | Antisense compounds for inducing axon termination and preparations containing them for the treatment of muscular dystrophy |
| IL297299A (en) * | 2009-11-12 | 2022-12-01 | Univ Western Australia | Antisense oligonucleotides for inducing exon skipping in the dystrophin gene |
| CN107353317A (zh) | 2010-05-28 | 2017-11-17 | 萨勒普塔医疗公司 | 具有修饰的亚基间键和/或端基的寡核苷酸类似物 |
| TWI541024B (zh) * | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
| US9161948B2 (en) * | 2011-05-05 | 2015-10-20 | Sarepta Therapeutics, Inc. | Peptide oligonucleotide conjugates |
| KR102229650B1 (ko) | 2011-05-05 | 2021-03-19 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 펩타이드 올리고뉴클레오타이드 접합체 |
| WO2013033407A2 (en) * | 2011-08-30 | 2013-03-07 | The Regents Of The University Of California | Identification of small molecules that enhance therapeutic exon skipping |
| CN112251436A (zh) * | 2012-01-27 | 2021-01-22 | 比奥马林技术公司 | 治疗杜兴型肌营养不良症和贝克型肌营养不良症的具有改善特性的rna调节性寡核苷酸 |
| EA031110B1 (ru) * | 2012-03-20 | 2018-11-30 | Сарепта Терапьютикс, Инк. | Конъюгаты бороновых кислот олигонуклеотидных аналогов |
| WO2014100714A1 (en) * | 2012-12-20 | 2014-06-26 | Sarepta Therapeutics, Inc. | Improved exon skipping compositions for treating muscular dystrophy |
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