CN119280261A - 使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 - Google Patents
使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 Download PDFInfo
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Applications Claiming Priority (20)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962805271P | 2019-02-13 | 2019-02-13 | |
| US62/805,271 | 2019-02-13 | ||
| US201962850919P | 2019-05-21 | 2019-05-21 | |
| US62/850,919 | 2019-05-21 | ||
| US201962852228P | 2019-05-23 | 2019-05-23 | |
| US201962852224P | 2019-05-23 | 2019-05-23 | |
| US62/852,228 | 2019-05-23 | ||
| US62/852,224 | 2019-05-23 | ||
| US201962873138P | 2019-07-11 | 2019-07-11 | |
| US62/873,138 | 2019-07-11 | ||
| US201962888867P | 2019-08-19 | 2019-08-19 | |
| US62/888,867 | 2019-08-19 | ||
| US201962931722P | 2019-11-06 | 2019-11-06 | |
| US62/931,722 | 2019-11-06 | ||
| US201962941569P | 2019-11-27 | 2019-11-27 | |
| US62/941,569 | 2019-11-27 | ||
| US202062966526P | 2020-01-27 | 2020-01-27 | |
| US62/966,526 | 2020-01-27 | ||
| PCT/US2020/018073 WO2020168051A1 (en) | 2019-02-13 | 2020-02-13 | Methods of editing a disease-associated gene using adenosine deaminase base editors, including for the treatment of genetic disease |
| CN202080028186.5A CN114040970B (zh) | 2019-02-13 | 2020-02-13 | 使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202080028186.5A Division CN114040970B (zh) | 2019-02-13 | 2020-02-13 | 使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 |
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|---|---|
| CN119280261A true CN119280261A (zh) | 2025-01-10 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411269394.0A Pending CN119280261A (zh) | 2019-02-13 | 2020-02-13 | 使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 |
| CN202080028186.5A Active CN114040970B (zh) | 2019-02-13 | 2020-02-13 | 使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN202080028186.5A Active CN114040970B (zh) | 2019-02-13 | 2020-02-13 | 使用腺苷脱氨酶碱基编辑器编辑疾病相关基因的方法，包括遗传性疾病的治疗 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20230140953A1 (https=) |
| EP (1) | EP3924484A4 (https=) |
| JP (2) | JP7586601B2 (https=) |
| KR (1) | KR20210127206A (https=) |
| CN (2) | CN119280261A (https=) |
| AU (1) | AU2020223306A1 (https=) |
| CA (1) | CA3128876A1 (https=) |
| WO (1) | WO2020168051A1 (https=) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3765615T3 (pl) | 2018-03-14 | 2023-11-13 | Arbor Biotechnologies, Inc. | Nowe enzymy i układy crispr ukierunkowane na dna |
| CN121555430A (zh) | 2018-05-11 | 2026-02-24 | 比姆医疗股份有限公司 | 使用可编程碱基编辑器系统取代病原性氨基酸的方法 |
| US12522812B2 (en) | 2018-05-16 | 2026-01-13 | Arbor Biotechnologies, Inc. | CRISPR-associated systems and components |
| KR20210055733A (ko) | 2018-09-07 | 2021-05-17 | 빔 테라퓨틱스, 인크. | 핵염기 편집 시스템을 전달하기 위한 조성물 및 방법 |
| EP3850088A4 (en) | 2018-09-07 | 2023-07-19 | Beam Therapeutics, Inc. | Compositions and methods for improving base editing |
| US20220235347A1 (en) | 2019-02-13 | 2022-07-28 | Beam Therapeutics Inc. | Compositions and methods for treating hemoglobinopathies |
| WO2020168122A1 (en) | 2019-02-13 | 2020-08-20 | Beam Therapeutics Inc. | Modified immune cells having adenosine deaminase base editors for modifying a nucleobase in a target sequence |
| KR102851101B1 (ko) | 2019-04-15 | 2025-08-27 | 에디진 테라퓨틱스(베이징) 인크. | Rna를 편집하기 위한 방법 및 조성물 |
| PE20220300A1 (es) | 2019-07-12 | 2022-03-09 | Univ Beijing | Edicion de acido ribonucleico (arn) dirigido aprovechando la adenosina desaminasa que actua sobre acido ribonucleico endogeno (adar) utilizando acidos ribonucleicos (arn) modificados geneticamente |
| EP4034138A4 (en) | 2019-09-27 | 2024-07-31 | Beam Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIQUID CANCERS |
| IL294201A (en) * | 2019-12-30 | 2022-08-01 | Edigene Therapeutics Beijing Inc | A method based on leaper technology to treat mps ih and a preparation |
| CA3170326A1 (en) * | 2020-02-13 | 2021-08-19 | Beam Therapeutics Inc. | Compositions and methods for engraftment of base edited cells |
| WO2022027035A1 (en) * | 2020-07-27 | 2022-02-03 | The Children's Hospital Of Philadelphia | In utero and postnatal gene editing and therapy for treatment of monogenic diseases, including mucopolysaccharidosis type 1h and other disorders |
| AU2021347359A1 (en) | 2020-09-25 | 2023-05-18 | Beam Therapeutics Inc. | Fratricide resistant modified immune cells and methods of using the same |
| CA3196425A1 (en) * | 2020-10-21 | 2022-04-28 | Jin Billy Li | A screening platform for adar-recruiting guide rnas |
| WO2022221699A1 (en) * | 2021-04-16 | 2022-10-20 | Beam Therapeutics, Inc. | Genetic modification of hepatocytes |
| WO2022241270A2 (en) * | 2021-05-14 | 2022-11-17 | Beam Therapeutics Inc. | Compositions and methods for treating transthyretin amyloidosis |
| WO2022246266A1 (en) * | 2021-05-21 | 2022-11-24 | Beam Therapeutics Inc. | Base editing of transthyretin gene |
| EP4426821A1 (en) * | 2021-11-02 | 2024-09-11 | University of Massachusetts | Nme2cas9 inlaid domain fusion proteins |
| EP4441219A2 (en) * | 2021-12-01 | 2024-10-09 | Shape Therapeutics Inc. | Engineered guide rnas and polynucleotides for rna editing targeting lrrk2 |
| WO2023169454A1 (zh) * | 2022-03-08 | 2023-09-14 | 中国科学院遗传与发育生物学研究所 | 腺嘌呤脱氨酶及其在碱基编辑中的用途 |
| CN114686456B (zh) * | 2022-05-10 | 2023-02-17 | 中山大学 | 基于双分子脱氨酶互补的碱基编辑系统及其应用 |
| KR20250067157A (ko) * | 2022-09-08 | 2025-05-14 | 더 유니버시티 코트 오브 더 유니버시티 오브 에딘버그 | 레트 증후군 요법 |
| WO2024230760A1 (zh) * | 2023-05-09 | 2024-11-14 | 北京齐禾生科生物科技有限公司 | 一种可作用于dna的腺苷脱氨酶及其应用 |
| WO2024233941A1 (en) * | 2023-05-11 | 2024-11-14 | Massachusetts Eye And Ear Infirmary | Base editing approaches to treat abca4-associated stargardt disease |
| WO2024238623A1 (en) * | 2023-05-15 | 2024-11-21 | University Of Georgia Research Foundation, Inc. | Doubly constrained peptides as allosteric inhibitors of leucine rich repeat kinase 2 |
| CN117965505A (zh) * | 2023-06-28 | 2024-05-03 | 微光基因(苏州)有限公司 | 工程化的腺苷脱氨酶及碱基编辑器 |
| CN120536418A (zh) * | 2024-02-26 | 2025-08-26 | 尧唐(上海)生物科技有限公司 | 一种脱氨酶变体、包含其的碱基编辑器及其应用 |
| WO2025184515A1 (en) * | 2024-02-29 | 2025-09-04 | Vesigen, Inc. | Arrdc1-mediated microvesicle-based delivery of therapeutic agents to cells and tissues of the eye |
Family Cites Families (8)
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|---|---|---|---|---|
| US20130109048A1 (en) * | 2010-07-09 | 2013-05-02 | Ecole Polytechnique Federale De Lausanne (Epfl) | Method for in-vitro monitoring of neuronal disorders and use thereof |
| ES2753391T3 (es) * | 2014-10-14 | 2020-04-08 | Halozyme Inc | Composiciones de adenosina desaminasa 2 (ADA2), variantes de la misma y métodos de uso de las mismas |
| KR102547316B1 (ko) * | 2016-08-03 | 2023-06-23 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 아데노신 핵염기 편집제 및 그의 용도 |
| EP3526320A1 (en) * | 2016-10-14 | 2019-08-21 | President and Fellows of Harvard College | Aav delivery of nucleobase editors |
| WO2018213708A1 (en) * | 2017-05-18 | 2018-11-22 | The Broad Institute, Inc. | Systems, methods, and compositions for targeted nucleic acid editing |
| AU2018290843B2 (en) * | 2017-06-26 | 2025-04-24 | Massachusetts Institute Of Technology | CRISPR/Cas-adenine deaminase based compositions, systems, and methods for targeted nucleic acid editing |
| CN109306361B (zh) * | 2018-02-11 | 2022-06-28 | 华东师范大学 | 一种新的a/t到g/c碱基定点转换的基因编辑系统 |
| CN109295186B (zh) * | 2018-09-30 | 2023-10-03 | 中山大学 | 一种基于全基因组测序检测腺嘌呤单碱基编辑系统脱靶效应的方法及其在基因编辑中的应用 |
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