CN118530993A - 用于ttr基因编辑及治疗attr淀粉样变性的组合物及方法 - Google Patents
用于ttr基因编辑及治疗attr淀粉样变性的组合物及方法 Download PDFInfo
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12491261B2 (en) | 2016-10-26 | 2025-12-09 | Acuitas Therapeutics, Inc. | Lipid nanoparticle formulations |
| MX394999B (es) | 2017-09-29 | 2025-03-24 | Regeneron Pharma | Animales no humanos que comprenden un locus ttr humanizado y metodos de uso |
| JP7543259B2 (ja) | 2018-10-18 | 2024-09-02 | アクイタス セラピューティクス インコーポレイテッド | 活性剤の脂質ナノ粒子送達のための脂質 |
| AU2020248337A1 (en) * | 2019-03-28 | 2021-11-04 | Intellia Therapeutics, Inc. | Compositions and methods for ttr gene editing and treating ATTR amyloidosis comprising a corticosteroid or use thereof |
| EP3946598A1 (en) * | 2019-03-28 | 2022-02-09 | Intellia Therapeutics, Inc. | Compositions and methods comprising a ttr guide rna and a polynucleotide encoding an rna-guided dna binding agent |
| BR112021019224A2 (pt) * | 2019-03-28 | 2021-11-30 | Intellia Therapeutics Inc | Polinucleotídeos, composições e métodos para expressão de polipeptídeo |
| US11891618B2 (en) | 2019-06-04 | 2024-02-06 | Regeneron Pharmaceuticals, Inc. | Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use |
| MX2022006950A (es) * | 2019-12-11 | 2022-11-07 | Intellia Therapeutics Inc | Arn guía modificados para edición de genes. |
| EP4237005A4 (en) * | 2020-10-28 | 2024-10-09 | Novo Nordisk A/S | ANTI-TRANSTHYRETIN ANTIBODIES AND METHODS OF USE THEREOF |
| CR20230305A (es) | 2020-12-11 | 2023-11-10 | Intellia Therapeutics Inc | Polinucleótidos, composiciones y métodos para la edición del genoma que implican desaminación |
| CN112795595A (zh) * | 2020-12-24 | 2021-05-14 | 中山大学 | 一种遗传性转甲状腺素蛋白淀粉样变性疾病的基因治疗系统 |
| WO2022246266A1 (en) * | 2021-05-21 | 2022-11-24 | Beam Therapeutics Inc. | Base editing of transthyretin gene |
| KR20240038705A (ko) | 2021-06-22 | 2024-03-25 | 인텔리아 테라퓨틱스, 인크. | 간 유전자의 생체 내 편집 방법 |
| US20250127927A1 (en) * | 2021-08-23 | 2025-04-24 | The Board Of Trustees Of The Leland Stanford Junior University | Targeted integration at beta-globin locus in human hematopoietic stem and progenitor cells |
| AU2022345881A1 (en) | 2021-09-20 | 2024-03-21 | Alnylam Pharmaceuticals, Inc. | Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof |
| CN116064598B (zh) * | 2021-10-08 | 2024-03-12 | 苏州艾博生物科技有限公司 | 冠状病毒的核酸疫苗 |
| WO2023185697A2 (en) * | 2022-03-29 | 2023-10-05 | Accuredit Therapeutics (Suzhou) Co., Ltd. | Compositions and methods for treatment of transthyretin amyloidosis |
| WO2024003805A1 (en) * | 2022-06-30 | 2024-01-04 | Geneditbio Limited | Methods and compositions for ttr gene editing and therapy using crispr system |
| TW202417017A (zh) * | 2022-06-30 | 2024-05-01 | 香港商正基基因科技有限公司 | 具有化學修飾的導引rna |
| CN118853659A (zh) * | 2023-04-14 | 2024-10-29 | 深圳瑞吉生物科技有限公司 | 提高mRNA翻译蛋白的输出量的核酸及其应用 |
| WO2024259135A1 (en) | 2023-06-13 | 2024-12-19 | Intellia Therapeutics, Inc. | Assays for analysis of ribonucleic acid (rna) molecules |
| CN120265763A (zh) * | 2023-10-25 | 2025-07-04 | 上海津曼特生物科技有限公司 | 靶向ttr的基因编辑组合物 |
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Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| KR940703846A (ko) | 1991-12-24 | 1994-12-12 | 비. 린네 파샬 | 갭(gap)이 형성된 2′ 변성된 올리고뉴클레오티드(gapped 2′ modifed oligonucleotides) |
| US6169169B1 (en) | 1994-05-19 | 2001-01-02 | Dako A/S | PNA probes for detection of Neisseria gonorrhoeae and Chlamydia trachomatis |
| US6974667B2 (en) | 2000-06-14 | 2005-12-13 | Gene Logic, Inc. | Gene expression profiles in liver cancer |
| US7244764B2 (en) * | 2003-06-23 | 2007-07-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| WO2006007712A1 (en) | 2004-07-19 | 2006-01-26 | Protiva Biotherapeutics, Inc. | Methods comprising polyethylene glycol-lipid conjugates for delivery of therapeutic agents |
| WO2010017509A1 (en) | 2008-08-07 | 2010-02-11 | Isis Pharmaceuticals, Inc. | Modulation of transthyretin expression for the treatment of cns related disorders |
| EA036772B1 (ru) | 2008-10-20 | 2020-12-18 | Элнилэм Фармасьютикалз, Инк. | Композиции и способы для ингибирования экспрессии транстиретина |
| US9101643B2 (en) | 2009-11-03 | 2015-08-11 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of transthyretin (TTR) |
| RS56011B1 (sr) | 2010-04-29 | 2017-09-29 | Ionis Pharmaceuticals Inc | Modulacija ekspresije transtiretina |
| HUE048622T2 (hu) | 2011-11-18 | 2020-08-28 | Alnylam Pharmaceuticals Inc | RNSi szerek, készítmények és alkalmazási eljárások transztiretin (TTR) asszociált betegségek kezelésére |
| WO2014093694A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes |
| DK2931897T3 (en) * | 2012-12-12 | 2018-02-05 | Broad Inst Inc | CONSTRUCTION, MODIFICATION AND OPTIMIZATION OF SYSTEMS, PROCEDURES AND COMPOSITIONS FOR SEQUENCE MANIPULATION AND THERAPEUTICAL APPLICATIONS |
| DK2931898T3 (en) | 2012-12-12 | 2016-06-20 | Massachusetts Inst Technology | CONSTRUCTION AND OPTIMIZATION OF SYSTEMS, PROCEDURES AND COMPOSITIONS FOR SEQUENCE MANIPULATION WITH FUNCTIONAL DOMAINS |
| CA2895155C (en) | 2012-12-17 | 2021-07-06 | President And Fellows Of Harvard College | Rna-guided human genome engineering |
| EP3608308B1 (en) | 2013-03-08 | 2021-07-21 | Novartis AG | Lipids and lipid compositions for the delivery of active agents |
| SI2986729T1 (sl) | 2013-04-16 | 2019-02-28 | Regeneron Pharmaceuticals, Inc. | Ciljana sprememba genoma podgane |
| DK2991656T3 (da) | 2013-05-01 | 2020-03-23 | Ionis Pharmaceuticals Inc | Sammensætninger og fremgangsmåder til modulering af apolipoprotein c-iii-ekspression |
| KR20160019553A (ko) * | 2013-06-17 | 2016-02-19 | 더 브로드 인스티튜트, 인코퍼레이티드 | 유사분열 후 세포의 질병 및 장애를 표적화하고 모델링하기 위한 시스템, 방법 및 조성물의 전달, 유전자 조작 및 최적화 |
| US20150165054A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting caspase-9 point mutations |
| ES2895651T3 (es) | 2013-12-19 | 2022-02-22 | Novartis Ag | Lípidos y composiciones lipídicas para la administración de agentes activos |
| CN106687601A (zh) * | 2014-05-28 | 2017-05-17 | 株式会社图尔金 | 使用靶特异性核酸酶灵敏检测靶dna的方法 |
| KR102386101B1 (ko) * | 2014-06-26 | 2022-04-14 | 리제너론 파마슈티칼스 인코포레이티드 | 표적화된 유전자 변형을 위한 방법 및 그 조성물, 및 사용 방법 |
| EP3169309B1 (en) | 2014-07-16 | 2023-05-10 | Novartis AG | Method of encapsulating a nucleic acid in a lipid nanoparticle host |
| EP3265559B1 (en) | 2015-03-03 | 2021-01-06 | The General Hospital Corporation | Engineered crispr-cas9 nucleases with altered pam specificity |
| WO2017053431A2 (en) * | 2015-09-21 | 2017-03-30 | Arcturus Therapeutics, Inc. | Allele selective gene editing and uses thereof |
| ES2964690T3 (es) | 2015-09-21 | 2024-04-09 | Trilink Biotechnologies Llc | Método para sintetizar ARN con caperuza 5' |
| CA2999649A1 (en) * | 2015-11-06 | 2017-05-11 | Crispr Therapeutics Ag | Materials and methods for treatment of glycogen storage disease type 1a |
| CA3006618A1 (en) * | 2015-12-01 | 2017-06-08 | Crispr Therapeutics Ag | Materials and methods for treatment of alpha-1 antitrypsin deficiency |
| US11083799B2 (en) * | 2016-03-16 | 2021-08-10 | Crispr Therapeutics Ag | Materials and methods for treatment of hereditary haemochromatosis |
| TWI773666B (zh) * | 2016-03-30 | 2022-08-11 | 美商英特利亞醫療公司 | Crispr/cas 組分之脂質奈米粒子調配物 |
| WO2018007871A1 (en) * | 2016-07-08 | 2018-01-11 | Crispr Therapeutics Ag | Materials and methods for treatment of transthyretin amyloidosis |
| AU2017374044B2 (en) | 2016-12-08 | 2023-11-30 | Intellia Therapeutics, Inc. | Modified guide RNAs |
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