IL303230A - Compositions and methods for treating facioscapulohumeral muscular dystrophy (fshd) - Google Patents
Compositions and methods for treating facioscapulohumeral muscular dystrophy (fshd)Info
- Publication number
- IL303230A IL303230A IL303230A IL30323023A IL303230A IL 303230 A IL303230 A IL 303230A IL 303230 A IL303230 A IL 303230A IL 30323023 A IL30323023 A IL 30323023A IL 303230 A IL303230 A IL 303230A
- Authority
- IL
- Israel
- Prior art keywords
- dux4
- aav
- vector
- nucleic acid
- promoter
- Prior art date
Links
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| US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
| EP0733103B1 (en) | 1993-11-09 | 2004-03-03 | Targeted Genetics Corporation | Generation of high titers of recombinant aav vectors |
| DE69433922T2 (de) | 1993-11-09 | 2005-07-28 | Medical College Of Ohio, Toledo | Stabile zellinie, die in der lage ist, das replikationsgen des adenoassoziertenvirus zu exprimieren |
| US5658785A (en) | 1994-06-06 | 1997-08-19 | Children's Hospital, Inc. | Adeno-associated virus materials and methods |
| US5856152A (en) | 1994-10-28 | 1999-01-05 | The Trustees Of The University Of Pennsylvania | Hybrid adenovirus-AAV vector and methods of use therefor |
| WO1996017947A1 (en) | 1994-12-06 | 1996-06-13 | Targeted Genetics Corporation | Packaging cell lines for generation of high titers of recombinant aav vectors |
| FR2737730B1 (fr) | 1995-08-10 | 1997-09-05 | Pasteur Merieux Serums Vacc | Procede de purification de virus par chromatographie |
| JPH11511326A (ja) | 1995-08-30 | 1999-10-05 | ジエンザイム コーポレイション | アデノウィルスおよびａａｖの精製 |
| JPH11514853A (ja) | 1995-09-08 | 1999-12-21 | ジエンザイム コーポレイション | 遺伝子治療のための改良されたａａｖベクター |
| US5910434A (en) | 1995-12-15 | 1999-06-08 | Systemix, Inc. | Method for obtaining retroviral packaging cell lines producing high transducing efficiency retroviral supernatant |
| EP1696036B1 (en) | 1996-09-06 | 2010-04-21 | The Trustees of The University of Pennsylvania | Use of recombinant adeno-associated virus in the manufacture of a medicament for gene therapy via muscle cells |
| CA2995542A1 (en) | 1997-09-05 | 1999-03-11 | Genzyme Corporation | Methods for generating high titer helper-free preparations of recombinant aav vectors |
| US6566118B1 (en) | 1997-09-05 | 2003-05-20 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| US6258595B1 (en) | 1999-03-18 | 2001-07-10 | The Trustees Of The University Of Pennsylvania | Compositions and methods for helper-free production of recombinant adeno-associated viruses |
| JP2004514407A (ja) | 2000-04-28 | 2004-05-20 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 異種キャプシド中にシュードタイピングされたａａｖ５キャプシドおよびａａｖ５ベクターを含む組換えａａｖベクター |
| WO2002053703A2 (en) | 2001-01-05 | 2002-07-11 | Children's Hospital, Inc. | Aav2 vectors and methods |
| DK2359869T3 (en) | 2001-12-17 | 2019-04-15 | Univ Pennsylvania | Sequences of adeno-associated virus (AAV) serotype 8, vectors containing these, and uses thereof |
| CA2842798C (en) | 2011-07-25 | 2021-02-23 | Nationwide Children's Hospital, Inc. | Recombinant virus products and methods for inhibition of expression of dux4 |
| DE102012007232B4 (de) | 2012-04-07 | 2014-03-13 | Susanne Weller | Verfahren zur Herstellung von rotierenden elektrischen Maschinen |
| JP2015092462A (ja) | 2013-09-30 | 2015-05-14 | Tdk株式会社 | 正極及びそれを用いたリチウムイオン二次電池 |
| WO2015141521A1 (ja) | 2014-03-21 | 2015-09-24 | 株式会社日立国際電気 | 基板処理装置、半導体装置の製造方法及び記録媒体 |
| JP6197169B2 (ja) | 2014-09-29 | 2017-09-20 | 東芝メモリ株式会社 | 半導体装置の製造方法 |
| JP6966463B2 (ja) * | 2016-02-26 | 2021-11-17 | リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル | 組換えウイルス産物及びｄｕｘ４エクソンスキッピングを誘導するための方法 |
| WO2020028134A1 (en) * | 2018-07-30 | 2020-02-06 | Fred Hutchinson Cancer Research Center | Methods and compositions for treating cancer |
| JP2022516515A (ja) * | 2018-12-31 | 2022-02-28 | リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル | Ｒｎａ標的化ｃｒｉｓｐｒ－ｃａｓ１３ｂを使用するｄｕｘ４ ｒｎａ発現停止 |
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2021
- 2021-11-30 CA CA3203585A patent/CA3203585A1/en active Pending
- 2021-11-30 WO PCT/US2021/061109 patent/WO2022115745A1/en not_active Ceased
- 2021-11-30 JP JP2023532456A patent/JP2023551279A/ja active Pending
- 2021-11-30 EP EP21830568.8A patent/EP4251752A1/en active Pending
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- 2021-11-30 AU AU2021385595A patent/AU2021385595A1/en active Pending
- 2021-11-30 US US18/038,878 patent/US20240026356A1/en active Pending
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|---|---|
| CA3203585A1 (en) | 2022-06-02 |
| EP4251752A1 (en) | 2023-10-04 |
| KR20230128470A (ko) | 2023-09-05 |
| WO2022115745A1 (en) | 2022-06-02 |
| AU2021385595A1 (en) | 2023-06-29 |
| AU2021385595A9 (en) | 2023-08-17 |
| JP2023551279A (ja) | 2023-12-07 |
| US20240026356A1 (en) | 2024-01-25 |
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