KR20230129996A - 탈아미노화를 포함하는 게놈 편집을 위한 폴리뉴클레오타이드,조성물 및 방법 - Google Patents
탈아미노화를 포함하는 게놈 편집을 위한 폴리뉴클레오타이드,조성물 및 방법 Download PDFInfo
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- 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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- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12Q2521/00—Reaction characterised by the enzymatic activity
- C12Q2521/50—Other enzymatic activities
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- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/US2021/062922 WO2022125968A1 (en) | 2020-12-11 | 2021-12-10 | Polynucleotides, compositions, and methods for genome editing involving deamination |
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| WO2022246266A1 (en) * | 2021-05-21 | 2022-11-24 | Beam Therapeutics Inc. | Base editing of transthyretin gene |
| WO2022261292A1 (en) * | 2021-06-10 | 2022-12-15 | Intellia Therapeutics, Inc. | Modified guide rnas comprising an internal linker for gene editing |
| IL312507A (en) * | 2021-11-03 | 2024-07-01 | Intellia Therapeutics Inc | Modified guide rnas for gene editing |
| CA3237303A1 (en) * | 2021-11-03 | 2023-05-11 | Intellia Therapeutics, Inc. | Polynucleotides, compositions, and methods for genome editing |
| WO2024006955A1 (en) | 2022-06-29 | 2024-01-04 | Intellia Therapeutics, Inc. | Engineered t cells |
| EP4638783A2 (en) | 2022-12-22 | 2025-10-29 | Intellia Therapeutics, Inc. | Methods for analyzing nucleic acid cargos of lipid nucleic acid assemblies |
| WO2024227082A1 (en) * | 2023-04-26 | 2024-10-31 | Vijay Sankaran | Base-editing perturbation screens and uses thereof |
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| WO2025038642A1 (en) | 2023-08-14 | 2025-02-20 | Intellia Therapeutics, Inc. | Compositions and methods for genetically modifying cd70 |
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Family Cites Families (30)
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|---|---|---|---|---|
| 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 |
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| US20060051405A1 (en) | 2004-07-19 | 2006-03-09 | Protiva Biotherapeutics, Inc. | Compositions for the delivery of therapeutic agents and uses thereof |
| US7774185B2 (en) | 2004-09-14 | 2010-08-10 | International Business Machines Corporation | Protein structure alignment using cellular automata |
| US20140310830A1 (en) | 2012-12-12 | 2014-10-16 | Feng Zhang | CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes |
| CN107879960B (zh) | 2013-03-08 | 2021-06-22 | 诺华股份有限公司 | 用于传递活性成分的脂质和脂质组合物 |
| US20150165054A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting caspase-9 point mutations |
| EP3083556B1 (en) | 2013-12-19 | 2019-12-25 | Novartis AG | Lipids and lipid compositions for the delivery of active agents |
| CN106794141B (zh) | 2014-07-16 | 2021-05-28 | 诺华股份有限公司 | 将核酸包封在脂质纳米粒主体中的方法 |
| KR20230156800A (ko) | 2015-03-03 | 2023-11-14 | 더 제너럴 하스피탈 코포레이션 | 변경된 PAM 특이성을 갖는 조작된 CRISPR-Cas9 뉴클레아제 |
| CN120842296A (zh) | 2015-09-21 | 2025-10-28 | 垂林克生物技术有限公司 | 用于合成5’-加帽rna的组合物和方法 |
| LT3436077T (lt) | 2016-03-30 | 2025-06-25 | Intellia Therapeutics, Inc. | Lipidų nanodalelių vaisto formos, skirtos crispr/cas komponentams |
| KR20180134412A (ko) | 2016-04-22 | 2018-12-18 | 인텔리아 테라퓨틱스, 인크. | 전사 인자 4에서 트라이뉴클레오타이드 반복부와 연관된 질환의 치료를 위한 조성물 및 방법 |
| SG10202106058WA (en) | 2016-12-08 | 2021-07-29 | Intellia Therapeutics Inc | Modified guide rnas |
| TWI851534B (zh) | 2016-12-22 | 2024-08-11 | 美商英特利亞醫療公司 | 用於治療α-１抗胰蛋白酶缺乏症之組合物及方法 |
| WO2019041296A1 (zh) * | 2017-09-01 | 2019-03-07 | 上海科技大学 | 一种碱基编辑系统及方法 |
| US20230140670A1 (en) | 2017-09-29 | 2023-05-04 | Intellia Therapeutics, Inc. | Formulations |
| EP3688161A1 (en) | 2017-09-29 | 2020-08-05 | Intellia Therapeutics, Inc. | Compositions and methods for ttr gene editing and treating attr amyloidosis |
| AU2019282824C1 (en) | 2018-06-08 | 2026-04-23 | Intellia Therapeutics, Inc. | Modified guide RNAS for gene editing |
| MX2021001070A (es) | 2018-07-31 | 2021-05-27 | Intellia Therapeutics Inc | Composiciones y métodos para editar el gen hidroxiácido oxidasa 1 (hao1) para tratar la hiperoxaluria primaria tipo 1 (ph1). |
| AU2019326408A1 (en) * | 2018-08-23 | 2021-03-11 | Sangamo Therapeutics, Inc. | Engineered target specific base editors |
| US20220009878A1 (en) | 2018-10-02 | 2022-01-13 | Intellia Therapeutics, Inc. | Ionizable amine lipids |
| IL282267B2 (en) | 2018-10-15 | 2026-03-01 | Univ Massachusetts | Programmed DNA editing by chimeric deaminase-nme2cas9 proteins |
| BR112021010853A2 (pt) | 2018-12-05 | 2021-08-31 | Intellia Therapeutics, Inc. | Lipídios de amina modificados |
| EP3911735A4 (en) * | 2019-01-16 | 2023-07-12 | Beam Therapeutics, Inc. | MODIFIED IMMUNE CELLS WITH INCREASED ANTINEOPLASTIC ACTIVITY AND RESISTANCE TO IMMUNOSUPPRESSION |
| 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 |
| CN114127044A (zh) | 2019-04-25 | 2022-03-01 | 英特利亚治疗股份有限公司 | 可电离的胺类脂质和脂质纳米颗粒 |
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- 2021-12-10 WO PCT/US2021/062922 patent/WO2022125968A1/en not_active Ceased
- 2021-12-10 CR CR20230305A patent/CR20230305A/es unknown
- 2021-12-10 MX MX2023006876A patent/MX2023006876A/es unknown
- 2021-12-10 TW TW110146322A patent/TW202237845A/zh unknown
- 2021-12-10 EP EP21852000.5A patent/EP4259792A1/en active Pending
- 2021-12-10 JP JP2023535332A patent/JP2023553935A/ja active Pending
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2023
- 2023-06-09 CL CL2023001684A patent/CL2023001684A1/es unknown
- 2023-06-09 US US18/332,335 patent/US20240002820A1/en active Pending
- 2023-07-07 CO CONC2023/0009114A patent/CO2023009114A2/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CO2023009114A2 (es) | 2023-08-18 |
| CL2023001684A1 (es) | 2024-01-05 |
| WO2022125968A1 (en) | 2022-06-16 |
| MX2023006876A (es) | 2023-07-31 |
| CA3205000A1 (en) | 2022-06-16 |
| IL303506A (en) | 2023-08-01 |
| EP4259792A1 (en) | 2023-10-18 |
| CR20230305A (es) | 2023-11-10 |
| TW202237845A (zh) | 2022-10-01 |
| AU2021394998A9 (en) | 2024-05-02 |
| JP2023553935A (ja) | 2023-12-26 |
| AU2021394998A1 (en) | 2023-06-29 |
| US20240002820A1 (en) | 2024-01-04 |
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