CA2479153C - Hybrid and single chain meganucleases and use thereof - Google Patents
Hybrid and single chain meganucleases and use thereof Download PDFInfo
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- CA2479153C CA2479153C CA2479153A CA2479153A CA2479153C CA 2479153 C CA2479153 C CA 2479153C CA 2479153 A CA2479153 A CA 2479153A CA 2479153 A CA2479153 A CA 2479153A CA 2479153 C CA2479153 C CA 2479153C
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- meganuclease
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- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36411302P | 2002-03-15 | 2002-03-15 | |
| US60/364,113 | 2002-03-15 | ||
| PCT/IB2003/001352 WO2003078619A1 (en) | 2002-03-15 | 2003-03-14 | Hybrid and single chain meganucleases and use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2479153A1 CA2479153A1 (en) | 2003-09-25 |
| CA2479153C true CA2479153C (en) | 2015-06-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2479153A Expired - Lifetime CA2479153C (en) | 2002-03-15 | 2003-03-14 | Hybrid and single chain meganucleases and use thereof |
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| Country | Link |
|---|---|
| US (2) | US8206965B2 (https=) |
| EP (1) | EP1485475B2 (https=) |
| JP (3) | JP2005520519A (https=) |
| AT (1) | ATE372379T1 (https=) |
| AU (1) | AU2003215869B2 (https=) |
| CA (1) | CA2479153C (https=) |
| DE (1) | DE60316124T3 (https=) |
| DK (1) | DK1485475T3 (https=) |
| ES (1) | ES2292994T3 (https=) |
| WO (1) | WO2003078619A1 (https=) |
Families Citing this family (160)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100151556A1 (en) * | 2002-03-15 | 2010-06-17 | Cellectis | Hybrid and single chain meganucleases and use thereof |
| WO2009095742A1 (en) * | 2008-01-31 | 2009-08-06 | Cellectis | New i-crei derived single-chain meganuclease and uses thereof |
| AU2003215869B2 (en) | 2002-03-15 | 2008-04-24 | Cellectis | Hybrid and single chain meganucleases and use thereof |
| EP3202899B1 (en) | 2003-01-28 | 2020-10-21 | Cellectis | Custom-made meganuclease and use thereof |
| US20070134796A1 (en) * | 2005-07-26 | 2007-06-14 | Sangamo Biosciences, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
| EP1591521A1 (en) | 2004-04-30 | 2005-11-02 | Cellectis | I-Dmo I derivatives with enhanced activity at 37 degrees C and use thereof |
| WO2007034262A1 (en) * | 2005-09-19 | 2007-03-29 | Cellectis | Heterodimeric meganucleases and use thereof |
| EP1863909B2 (en) | 2005-03-15 | 2014-09-10 | Cellectis | I-crei meganuclease variants with modified specificity, method of preparation and uses thereof |
| ES2582091T3 (es) | 2005-10-18 | 2016-09-09 | Precision Biosciences | Meganucleasas diseñadas racionalmente con especificidad de secuencia y afinidad de unión a ADN alteradas |
| WO2007049095A1 (en) | 2005-10-25 | 2007-05-03 | Cellectis | Laglidadg homing endonuclease variants having mutations in two functional subdomains and use thereof |
| WO2007060495A1 (en) | 2005-10-25 | 2007-05-31 | Cellectis | I-crei homing endonuclease variants having novel cleavage specificity and use thereof |
| WO2008010009A1 (en) * | 2006-07-18 | 2008-01-24 | Cellectis | Meganuclease variants cleaving a dna target sequence from a rag gene and uses thereof |
| WO2008093152A1 (en) * | 2007-02-01 | 2008-08-07 | Cellectis | Obligate heterodimer meganucleases and uses thereof |
| PL2602323T3 (pl) | 2007-06-01 | 2018-06-29 | Open Monoclonal Technology, Inc. | Kompozycje i sposoby hamowania endogennych genów immunoglobin i wytwarzania transgenicznych ludzkich przeciwciał typu idiotypowego |
| WO2008149176A1 (en) * | 2007-06-06 | 2008-12-11 | Cellectis | Meganuclease variants cleaving a dna target sequence from the mouse rosa26 locus and uses thereof |
| EP2770052A1 (en) | 2007-06-06 | 2014-08-27 | Cellectis | Method for enhancing the cleavage activity of I-CreI derived meganucleases |
| EP2167666A2 (en) | 2007-06-29 | 2010-03-31 | Pioneer Hi-Bred International Inc. | Methods for altering the genome of a monocot plant cell |
| WO2009013559A1 (en) | 2007-07-23 | 2009-01-29 | Cellectis | Meganuclease variants cleaving a dna target sequence from the human hemoglobin beta gene and uses thereof |
| WO2009019528A1 (en) * | 2007-08-03 | 2009-02-12 | Cellectis | Meganuclease variants cleaving a dna target sequence from the human interleukin-2 receptor gamma chain gene and uses thereof |
| US11235026B2 (en) | 2007-09-27 | 2022-02-01 | Sangamo Therapeutics, Inc. | Methods and compositions for modulating PD1 |
| EP2188384B1 (en) * | 2007-09-27 | 2015-07-15 | Sangamo BioSciences, Inc. | Rapid in vivo identification of biologically active nucleases |
| US8563314B2 (en) | 2007-09-27 | 2013-10-22 | Sangamo Biosciences, Inc. | Methods and compositions for modulating PD1 |
| EP2215223B1 (en) * | 2007-10-31 | 2013-05-01 | Precision Biosciences, Inc. | Rationally-designed single-chain meganucleases with non-palindromic recognition sequences |
| AU2015201270B2 (en) * | 2007-10-31 | 2017-01-19 | Precision Biosciences, Inc. | Rationally-designed single-chain meganucleases with non-palindromic recognition sequences |
| JP2011505809A (ja) * | 2007-12-07 | 2011-03-03 | プレシジョン バイオサイエンシズ，インク． | ヒトゲノムのＤＮａｓｅ高感受性領域に見出される認識配列を有する合理的に設計されたメガヌクレアーゼ |
| WO2009074842A1 (en) * | 2007-12-13 | 2009-06-18 | Cellectis | Improved chimeric meganuclease enzymes and uses thereof |
| WO2009114321A2 (en) * | 2008-03-11 | 2009-09-17 | Precision Biosciencs, Inc. | Rationally-designed meganucleases for maize genome engineering |
| US20100071083A1 (en) * | 2008-03-12 | 2010-03-18 | Smith James J | Temperature-dependent meganuclease activity |
| CA2722797A1 (en) * | 2008-04-28 | 2009-11-05 | Precision Biosciences, Inc. | Fusion molecules of rationally-designed dna-binding proteins and effector domains |
| EP2313498B1 (en) | 2008-07-14 | 2017-03-15 | Precision Biosciences, Inc. | Recognition sequences for i-crei-derived meganucleases and uses thereof |
| CN102177235A (zh) * | 2008-09-08 | 2011-09-07 | 赛莱克蒂斯公司 | 切割来自谷氨酰胺合成酶基因的dna靶序列的大范围核酸酶变体及其用途 |
| EP2180058A1 (en) | 2008-10-23 | 2010-04-28 | Cellectis | Meganuclease recombination system |
| EP2208785A1 (en) | 2009-01-15 | 2010-07-21 | Newbiotechnic, S.A. | Methods and kits to generate miRNA- and smallRNA-expressing vectors, and its application to develop lentiviral expression libraries |
| WO2010093966A2 (en) * | 2009-02-12 | 2010-08-19 | Fred Hutchinson Cancer Research Center | Generation of a dna nicking enzyme that stimulates site-specific gene conversion from a homing endonuclease |
| EP2408921B1 (en) | 2009-03-20 | 2017-04-19 | Sangamo BioSciences, Inc. | Modification of cxcr4 using engineered zinc finger proteins |
| WO2010122367A2 (en) * | 2009-04-21 | 2010-10-28 | Cellectis | Meganuclease variants cleaving the genomic insertion of a virus and uses thereof |
| US8772008B2 (en) | 2009-05-18 | 2014-07-08 | Sangamo Biosciences, Inc. | Methods and compositions for increasing nuclease activity |
| US20120171191A1 (en) | 2009-05-26 | 2012-07-05 | Cellectis | Meganuclease variants cleaving the genome of a pathogenic non-integrating virus and uses thereof |
| EP2449135B1 (en) | 2009-06-30 | 2016-01-06 | Sangamo BioSciences, Inc. | Rapid screening of biologically active nucleases and isolation of nuclease-modified cells |
| WO2011007193A1 (en) | 2009-07-17 | 2011-01-20 | Cellectis | Viral vectors encoding a dna repair matrix and containing a virion-associated site specific meganuclease for gene targeting |
| CA2769262C (en) | 2009-07-28 | 2019-04-30 | Sangamo Biosciences, Inc. | Methods and compositions for treating trinucleotide repeat disorders |
| US8586526B2 (en) | 2010-05-17 | 2013-11-19 | Sangamo Biosciences, Inc. | DNA-binding proteins and uses thereof |
| JP5940977B2 (ja) | 2009-08-11 | 2016-06-29 | サンガモ バイオサイエンシーズ， インコーポレイテッド | 標的改変によるホモ接合生物 |
| WO2011021062A1 (en) | 2009-08-21 | 2011-02-24 | Cellectis | Meganuclease variants cleaving a dna target sequence from the human lysosomal acid alpha-glucosidase gene and uses thereof |
| EP2480659A2 (en) | 2009-09-24 | 2012-08-01 | Cellectis | Meganuclease reagents of uses thereof for treating genetic diseases caused by frame shift/non sense mutations |
| AU2010325563B2 (en) | 2009-11-27 | 2017-02-02 | Basf Plant Science Company Gmbh | Chimeric endonucleases and uses thereof |
| CN102762726A (zh) | 2009-11-27 | 2012-10-31 | 巴斯夫植物科学有限公司 | 嵌合内切核酸酶及其用途 |
| WO2011082310A2 (en) | 2009-12-30 | 2011-07-07 | Pioneer Hi-Bred International, Inc. | Methods and compositions for targeted polynucleotide modification |
| WO2011095475A1 (en) * | 2010-02-02 | 2011-08-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the diagnosis and therapy of retinitis pigmentosa |
| WO2011101696A1 (en) | 2010-02-18 | 2011-08-25 | Cellectis | Improved meganuclease recombination system |
| WO2011104382A1 (en) | 2010-02-26 | 2011-09-01 | Cellectis | Use of endonucleases for inserting transgenes into safe harbor loci |
| CA2794037A1 (en) | 2010-03-22 | 2011-09-29 | Philip Morris Products S.A. | Modifying enzyme activity in plants |
| CA2799095A1 (en) | 2010-05-12 | 2011-11-17 | Cellectis | Meganuclease variants cleaving a dna target sequence from the dystrophin gene and uses thereof |
| US20130183282A1 (en) | 2010-05-12 | 2013-07-18 | Cellectis | Meganuclease variants cleaving a DNA target sequence from the rhodopsin gene and uses thereof |
| SG186372A1 (en) | 2010-06-15 | 2013-01-30 | Cellectis | Method for improving cleavage of dna by endonuclease sensitive to methylation |
| US20130189759A1 (en) | 2010-07-07 | 2013-07-25 | Cellectis | Meganucleases variants cleaving a dna target sequence in the nanog gene and uses thereof |
| WO2012010976A2 (en) | 2010-07-15 | 2012-01-26 | Cellectis | Meganuclease variants cleaving a dna target sequence in the tert gene and uses thereof |
| WO2012007848A2 (en) | 2010-07-16 | 2012-01-19 | Cellectis | Meganuclease variants cleaving a dna target sequence in the was gene and uses thereof |
| WO2012017329A2 (en) | 2010-08-02 | 2012-02-09 | Cellectis S.A. | Method for targeted genomic events in algae |
| US20130337454A1 (en) | 2010-10-27 | 2013-12-19 | Philippe Duchateau | Method for increasing the efficiency of double-strand break-induced mutagenesis |
| US9044492B2 (en) | 2011-02-04 | 2015-06-02 | Cellectis Sa | Method for modulating the efficiency of double-strand break-induced mutagenesis |
| CA2831144A1 (en) | 2011-03-23 | 2012-09-27 | Pioneer Hi-Bred International, Inc. | Methods for producing a complex transgenic trait locus |
| WO2012138901A1 (en) | 2011-04-05 | 2012-10-11 | Cellectis Sa | Method for enhancing rare-cutting endonuclease efficiency and uses thereof |
| CA3111953C (en) | 2011-04-05 | 2023-10-24 | Cellectis | Method for the generation of compact tale-nucleases and uses thereof |
| AU2012249390B2 (en) | 2011-04-27 | 2017-03-30 | Amyris, Inc. | Methods for genomic modification |
| WO2012158778A1 (en) | 2011-05-16 | 2012-11-22 | Cellectis S.A. | Doubly secure transgenic algae or cyanobacteria strains to prevent their establishment and spread in natural ecosystems |
| BR112013030652A2 (pt) | 2011-06-10 | 2016-12-13 | Basf Plant Science Co Gmbh | polinucleotídeo que codifica um polipeptídeo, molécula de ácido nucleico, vetor, organismo não humano, polipeptídeo e método para introduzir um ácido nucleico de interesse em um genoma de um organismo não humano |
| CA2844470A1 (en) | 2011-06-21 | 2013-05-10 | Pioneer Hi-Bred International, Inc. | Methods and compositions for producing male sterile plants |
| EP2729567B1 (en) | 2011-07-08 | 2016-10-05 | Cellectis | Method for increasing the efficiency of double-strand break-induced mutagenssis |
| EP2739739A1 (en) | 2011-08-03 | 2014-06-11 | E. I. Du Pont de Nemours and Company | Methods and compositions for targeted integration in a plant |
| WO2013130824A1 (en) | 2012-02-29 | 2013-09-06 | Sangamo Biosciences, Inc. | Methods and compositions for treating huntington's disease |
| US20150184173A1 (en) | 2012-05-04 | 2015-07-02 | E I Du Pont De Nemours And Company | Compositions and methods comprising sequences having meganuclease activity |
| EP2877488B1 (en) | 2012-07-24 | 2021-02-24 | Cellectis | New modular base-specific nucleic acid binding domains from burkholderia rhizoxinica proteins |
| AU2013329186B2 (en) | 2012-10-10 | 2019-02-14 | Sangamo Therapeutics, Inc. | T cell modifying compounds and uses thereof |
| CN105121649A (zh) | 2012-11-16 | 2015-12-02 | 赛莱蒂克斯公司 | 靶向修饰藻基因组的方法 |
| WO2014102688A1 (en) | 2012-12-27 | 2014-07-03 | Cellectis | New design matrix for improvement of homology-directed gene targeting |
| MX384291B (es) | 2013-02-20 | 2025-03-14 | Regeneron Pharma | Modificación genética de ratas. |
| RU2694686C2 (ru) | 2013-03-12 | 2019-07-16 | Е.И.Дюпон Де Немур Энд Компани | Способы идентификации вариантных сайтов распознавания для редкощепящих сконструированных средств для индукции двунитевого разрыва, и композиции с ними, и их применения |
| EP2970409A2 (en) | 2013-03-15 | 2016-01-20 | Bioven 3 Limited | Self-assembling synthetic proteins |
| DK3456831T3 (da) | 2013-04-16 | 2021-09-06 | Regeneron Pharma | Målrettet modifikation af rottegenom |
| WO2015070212A1 (en) | 2013-11-11 | 2015-05-14 | Sangamo Biosciences, Inc. | Methods and compositions for treating huntington's disease |
| EP3080279B1 (en) | 2013-12-11 | 2018-09-26 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for the targeted modification of a genome |
| KR102170502B1 (ko) | 2013-12-11 | 2020-10-28 | 리제너론 파마슈티칼스 인코포레이티드 | 게놈의 표적화된 변형을 위한 방법 및 조성물 |
| EP3083958B1 (en) | 2013-12-19 | 2019-04-17 | Amyris, Inc. | Methods for genomic integration |
| NZ759969A (en) | 2013-12-20 | 2022-12-23 | Fred Hutchinson Cancer Center | Tagged chimeric effector molecules and receptors thereof |
| CN106459894B (zh) | 2014-03-18 | 2020-02-18 | 桑格摩生物科学股份有限公司 | 用于调控锌指蛋白表达的方法和组合物 |
| HRP20200529T1 (hr) | 2014-06-06 | 2020-09-04 | Regeneron Pharmaceuticals, Inc. | Postupci i pripravci za modificiranje ciljnog lokusa |
| ES2781323T3 (es) | 2014-06-23 | 2020-09-01 | Regeneron Pharma | Montaje de ADN mediado por nucleasas |
| SI3161128T1 (sl) | 2014-06-26 | 2019-02-28 | Regeneron Pharmaceuticals, Inc. | Postopki in sestavki za ciljano genetsko spremembo in postopki uporabe |
| BR112017007770A2 (pt) | 2014-10-15 | 2018-01-16 | Regeneron Pharma | cultura in vitro, população de hipscs, método para modificar um locus-alvo genômico, e, hipsc. |
| ES2947714T3 (es) | 2014-12-19 | 2023-08-17 | Regeneron Pharma | Métodos y composiciones para la modificación genética dirigida a través de múltiples direccionamientos en un solo paso |
| CA2981077A1 (en) | 2015-04-03 | 2016-10-06 | Dana-Farber Cancer Institute, Inc. | Composition and methods of genome editing of b-cells |
| EP3288570A4 (en) | 2015-04-29 | 2018-11-21 | Fred Hutchinson Cancer Research Center | Modified stem cells and uses thereof |
| EP3389677B1 (en) | 2015-12-18 | 2024-06-26 | Sangamo Therapeutics, Inc. | Targeted disruption of the t cell receptor |
| BR112018012235A2 (pt) | 2015-12-18 | 2018-12-04 | Sangamo Therapeutics Inc | rompimento alvejado do receptor de células de mhc |
| US11293033B2 (en) | 2016-05-18 | 2022-04-05 | Amyris, Inc. | Compositions and methods for genomic integration of nucleic acids into exogenous landing pads |
| JP2019523009A (ja) | 2016-07-29 | 2019-08-22 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｃ末端切断型フィブリリン−１の発現をもたらす変異を有するマウス |
| KR102455249B1 (ko) | 2016-08-24 | 2022-10-17 | 상가모 테라퓨틱스, 인코포레이티드 | 가공된 표적 특이적 뉴클레아제 |
| CN109996868A (zh) | 2016-09-23 | 2019-07-09 | 弗雷德哈钦森癌症研究中心 | 特异性用于次要组织相容性(h)抗原ha-1的tcr及其用途 |
| IL268049B2 (en) | 2017-01-19 | 2025-08-01 | Omniab Inc | Transgenic rodent human antibodies with multiple immunoglobulin heavy chain loci |
| JP7037577B2 (ja) | 2017-03-15 | 2022-03-16 | フレッド ハッチンソン キャンサー リサーチ センター | 高親和性ｍａｇｅ－ａ１特異的ｔｃｒ及びその使用 |
| CN110799492B (zh) | 2017-04-28 | 2023-06-27 | 爱康泰生治疗公司 | 用于递送核酸的新型羰基脂质和脂质纳米颗粒制剂 |
| US11655275B2 (en) | 2017-05-03 | 2023-05-23 | Sangamo Therapeutics, Inc. | Methods and compositions for modification of a cystic fibrosis transmembrane conductance regulator (CFTR) gene |
| CA3064000A1 (en) | 2017-05-24 | 2018-11-29 | Effector Therapeutics, Inc. | Methods and compositions for cellular immunotherapy |
| US12398191B2 (en) | 2017-08-11 | 2025-08-26 | Fred Hutchinson Cancer Center | BRAF-specific TCRs and uses thereof |
| LT3675623T (lt) | 2017-08-29 | 2025-09-10 | KWS SAAT SE & Co. KGaA | Patobulintas mėlynasis aleuronas ir kitos segregacijos sistemos |
| CN111051349A (zh) | 2017-09-06 | 2020-04-21 | 弗雷德哈钦森癌症研究中心 | Strep-tag特异性嵌合受体及其用途 |
| US12350312B2 (en) | 2017-09-06 | 2025-07-08 | Fred Hutchinson Cancer Center | Methods for improving adoptive cell therapy |
| US20190098879A1 (en) | 2017-09-29 | 2019-04-04 | Regeneron Pharmaceuticals, Inc. | Non-Human Animals Comprising A Humanized TTR Locus And Methods Of Use |
| US20210069241A1 (en) | 2017-10-20 | 2021-03-11 | Fred Hutchinson Cancer Research Center | Compositions and methods of immunotherapy targeting tigit and/or cd112r or comprising cd226 overexpression |
| US20220267403A1 (en) | 2017-12-01 | 2022-08-25 | Fred Hutchinson Cancer Research Center | Binding proteins specific for 5t4 and uses thereof |
| WO2019140278A1 (en) | 2018-01-11 | 2019-07-18 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting core binding factor antigens |
| AU2019224051A1 (en) | 2018-02-26 | 2020-09-03 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
| US11332752B2 (en) | 2018-03-12 | 2022-05-17 | Pioneer Hi-Bred International, Inc. | Use of morphogenic factors for the improvement of gene editing |
| US11690921B2 (en) | 2018-05-18 | 2023-07-04 | Sangamo Therapeutics, Inc. | Delivery of target specific nucleases |
| WO2020018964A1 (en) | 2018-07-20 | 2020-01-23 | Fred Hutchinson Cancer Research Center | Compositions and methods for controlled expression of antigen-specific receptors |
| CN112912387A (zh) | 2018-08-22 | 2021-06-04 | 弗雷德哈钦森癌症研究中心 | 靶向kras或her2抗原的免疫疗法 |
| CA3110089A1 (en) | 2018-08-28 | 2020-03-05 | Fred Hutchinson Cancer Research Center | Methods and compositions for adoptive t cell therapy incorporating induced notch signaling |
| KR20210060533A (ko) | 2018-09-18 | 2021-05-26 | 상가모 테라퓨틱스, 인코포레이티드 | 프로그램화된 세포 사멸 1 (pd1) 특이적 뉴클레아제 |
| IL281615B2 (en) | 2018-09-21 | 2026-01-01 | Acuitas Therapeutics Inc | Systems and methods for producing lipid nanoparticles and liposomes |
| US20240165232A1 (en) | 2018-09-24 | 2024-05-23 | Fred Hutchinson Cancer Research Center | Chimeric receptor proteins and uses thereof |
| CA3116576A1 (en) | 2018-10-18 | 2020-04-23 | Acuitas Therapeutics, Inc. | Lipids for lipid nanoparticle delivery of active agents |
| CA3119188A1 (en) | 2018-11-09 | 2020-05-14 | Fred Hutchinson Cancer Research Center | T cell receptors specific for mesothelin and their use in immunotherapy |
| KR20200071198A (ko) | 2018-12-10 | 2020-06-19 | 네오이뮨텍, 인코퍼레이티드 | Nrf2 발현 조절 기반 T 세포 항암면역치료법 |
| KR102925054B1 (ko) | 2018-12-20 | 2026-02-10 | 리제너론 파마슈티칼스 인코포레이티드 | 뉴클레아제-매개 반복부 팽창 |
| PT3908568T (pt) | 2019-01-11 | 2024-09-30 | Acuitas Therapeutics Inc | Lípidos para a administração de agentes ativos por nanopartículas lipídicas |
| CN114026116A (zh) | 2019-02-20 | 2022-02-08 | 弗雷德哈钦森癌症研究中心 | Ras新抗原特异性结合蛋白及其用途 |
| WO2020185796A1 (en) | 2019-03-11 | 2020-09-17 | Fred Hutchinson Cancer Research Center | High avidity wt1 t cell receptors and uses thereof |
| RU2771374C1 (ru) | 2019-04-04 | 2022-05-04 | Редженерон Фармасьютикалс, Инк. | Способы для бесшовного внесения целевых модификаций в направленные векторы |
| KR102661779B1 (ko) | 2019-04-04 | 2024-04-30 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 응고 인자 12 좌위를 포함하는 비-인간 동물 |
| 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 |
| MX2021015122A (es) | 2019-06-07 | 2022-04-06 | Regeneron Pharma | Animales no humanos que comprenden un locus de albumina humanizado. |
| JP7737978B2 (ja) | 2019-08-20 | 2025-09-11 | フレッド ハッチンソン キャンサー センター | Ｗｔ－１に特異的なｔ細胞免疫療法 |
| WO2021108363A1 (en) | 2019-11-25 | 2021-06-03 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-mediated upregulation of humanized ttr allele |
| ES3054438T3 (en) | 2020-07-16 | 2026-02-03 | Acuitas Therapeutics Inc | Cationic lipids for use in lipid nanoparticles |
| US12152251B2 (en) | 2020-08-25 | 2024-11-26 | Kite Pharma, Inc. | T cells with improved functionality |
| CN116724053A (zh) | 2020-09-24 | 2023-09-08 | 弗雷德哈钦森癌症中心 | 靶向sox2抗原的免疫治疗 |
| WO2022066973A1 (en) | 2020-09-24 | 2022-03-31 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting pbk or oip5 antigens |
| WO2022076353A1 (en) | 2020-10-06 | 2022-04-14 | Fred Hutchinson Cancer Research Center | Compositions and methods for treating mage-a1-expressing disease |
| WO2022132836A2 (en) | 2020-12-14 | 2022-06-23 | Fred Hutchinson Cancer Research Center | Compositions and methods for cellular immunotherapy |
| CA3218511A1 (en) | 2021-05-10 | 2022-11-17 | Sqz Biotechnologies Company | Methods for delivering genome editing molecules to the nucleus or cytosol of a cell and uses thereof |
| WO2022251644A1 (en) | 2021-05-28 | 2022-12-01 | Lyell Immunopharma, Inc. | Nr4a3-deficient immune cells and uses thereof |
| EP4347826A1 (en) | 2021-06-02 | 2024-04-10 | Lyell Immunopharma, Inc. | Nr4a3-deficient immune cells and uses thereof |
| TW202317602A (zh) | 2021-07-15 | 2023-05-01 | 福瑞德哈金森腫瘤中心 | 嵌合多肽 |
| IL310550A (en) | 2021-08-04 | 2024-03-01 | Univ Colorado Regents | LAT-activating chimeric antigen receptor T cells and methods of using them |
| IL311962A (en) | 2021-10-14 | 2024-06-01 | Lonza Sales Ag | Modified producer cells for extracellular vesicle production |
| CA3237482A1 (en) | 2021-11-03 | 2023-05-11 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Precise genome editing using retrons |
| CA3242402A1 (en) | 2021-12-16 | 2023-06-22 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
| AU2022424002A1 (en) | 2021-12-29 | 2024-06-13 | Bristol-Myers Squibb Company | Generation of landing pad cell lines |
| WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| WO2023215725A1 (en) | 2022-05-02 | 2023-11-09 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
| US20250302998A1 (en) | 2022-05-09 | 2025-10-02 | Regeneron Pharmaceuticals, Inc. | Vectors and methods for in vivo antibody production |
| JP2025516823A (ja) | 2022-05-19 | 2025-05-30 | ライエル・イミュノファーマ・インコーポレイテッド | Ｎｒ４ａ３を標的とするポリヌクレオチド及びその使用 |
| WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| WO2024064952A1 (en) | 2022-09-23 | 2024-03-28 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells overexpressing c-jun |
| WO2024064958A1 (en) | 2022-09-23 | 2024-03-28 | Lyell Immunopharma, Inc. | Methods for culturing nr4a-deficient cells |
| WO2025054540A1 (en) | 2023-09-08 | 2025-03-13 | Iovance Biotherapeutics, Inc. | Methods of gene-editing using programmable nucleases |
| WO2025081123A1 (en) | 2023-10-12 | 2025-04-17 | Fred Hutchinson Cancer Center | Methods and compositions for improving t cell immunotherapy |
| WO2025101820A1 (en) | 2023-11-08 | 2025-05-15 | Fred Hutchinson Cancer Center | Compositions and methods for cellular immunotherapy |
| WO2025245169A1 (en) | 2024-05-21 | 2025-11-27 | Fred Hutchinson Cancer Center | Immunotherapy cells equipped with a collagen-targeting payload |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US5006333A (en) * | 1987-08-03 | 1991-04-09 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| FR2646438B1 (fr) * | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
| US5272071A (en) * | 1989-12-22 | 1993-12-21 | Applied Research Systems Ars Holding N.V. | Method for the modification of the expression characteristics of an endogenous gene of a given cell line |
| US5843701A (en) * | 1990-08-02 | 1998-12-01 | Nexstar Pharmaceticals, Inc. | Systematic polypeptide evolution by reverse translation |
| US6063630A (en) * | 1991-11-05 | 2000-05-16 | Transkaryotic Therapies, Inc. | Targeted introduction of DNA into primary or secondary cells and their use for gene therapy |
| US5641670A (en) * | 1991-11-05 | 1997-06-24 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| US5436150A (en) | 1992-04-03 | 1995-07-25 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoities (foki) restriction endonuclease |
| US20040019916A1 (en) * | 1992-04-24 | 2004-01-29 | Zarling David A. | In vivo homologous sequence targeting in eukaryotic cells |
| US5474896A (en) | 1992-05-05 | 1995-12-12 | Institut Pasteur | Nucleotide sequence encoding the enzyme I-SceI and the uses thereof |
| US5792632A (en) * | 1992-05-05 | 1998-08-11 | Institut Pasteur | Nucleotide sequence encoding the enzyme I-SceI and the uses thereof |
| US6395959B1 (en) * | 1992-05-05 | 2002-05-28 | Institut Pasteur | Nucleotide sequence encoding the enzyme I SceI and the use thereof |
| EP1340812B1 (en) | 1993-02-12 | 2011-06-15 | The Johns-Hopkins University | Functional domains in flavobacterium okeanokoites (Foki) restriction endonuclease |
| US5801030A (en) | 1995-09-01 | 1998-09-01 | Genvec, Inc. | Methods and vectors for site-specific recombination |
| US5830729A (en) | 1996-04-18 | 1998-11-03 | Institut Pasteur | I Sce I-induced gene replacement and gene conversion in embryonic stem cells |
| IL120241A0 (en) | 1997-02-17 | 1997-06-10 | B G Negev Technologies And App | DNA segments encoding a domain of ho-endonuclease |
| US6232112B1 (en) * | 1997-11-24 | 2001-05-15 | Flinders Technologies Pty Ltd Of Flinders University | Reagents and methods for diversification of DNA |
| CA2361191A1 (en) | 1999-02-03 | 2000-08-10 | The Children's Medical Center Corporation | Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site |
| EP1151124A1 (en) | 1999-02-03 | 2001-11-07 | The Children's Medical Center Corporation | Gene repair involving in vivo excision of targeting dna |
| WO2002068471A2 (en) * | 2000-12-21 | 2002-09-06 | Bristol-Myers Squibb Company | Nucleic acid molecules and polypeptides for a human cation channel polypeptide |
| DE10131786A1 (de) * | 2001-07-04 | 2003-01-16 | Sungene Gmbh & Co Kgaa | Rekombinationssysteme und Verfahren zum Entfernen von Nukleinsäuresequenzen aus dem Genom eukaryotischer Organismen |
| WO2003038444A2 (en) * | 2001-10-31 | 2003-05-08 | Pfizer Products Inc. | Biomarkers of liver function |
| AU2002360986A1 (en) * | 2001-12-20 | 2003-07-09 | Sungene Gmbh And Co. Kgaa | Methods for the transformation of vegetal plastids |
| AU2003215869B2 (en) | 2002-03-15 | 2008-04-24 | Cellectis | Hybrid and single chain meganucleases and use thereof |
| WO2009095742A1 (en) † | 2008-01-31 | 2009-08-06 | Cellectis | New i-crei derived single-chain meganuclease and uses thereof |
| EP3202899B1 (en) * | 2003-01-28 | 2020-10-21 | Cellectis | Custom-made meganuclease and use thereof |
| US7888121B2 (en) * | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| EP1591521A1 (en) | 2004-04-30 | 2005-11-02 | Cellectis | I-Dmo I derivatives with enhanced activity at 37 degrees C and use thereof |
| ES2582091T3 (es) † | 2005-10-18 | 2016-09-09 | Precision Biosciences | Meganucleasas diseñadas racionalmente con especificidad de secuencia y afinidad de unión a ADN alteradas |
| EP2167666A2 (en) † | 2007-06-29 | 2010-03-31 | Pioneer Hi-Bred International Inc. | Methods for altering the genome of a monocot plant cell |
| EP2215223B1 (en) † | 2007-10-31 | 2013-05-01 | Precision Biosciences, Inc. | Rationally-designed single-chain meganucleases with non-palindromic recognition sequences |
| WO2009074842A1 (en) † | 2007-12-13 | 2009-06-18 | Cellectis | Improved chimeric meganuclease enzymes and uses thereof |
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| US20040002092A1 (en) | 2004-01-01 |
| EP1485475B1 (en) | 2007-09-05 |
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| DE60316124D1 (de) | 2007-10-18 |
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| US8206965B2 (en) | 2012-06-26 |
| EP1485475B2 (en) | 2017-09-20 |
| CA2479153A1 (en) | 2003-09-25 |
| ES2292994T3 (es) | 2008-03-16 |
| JP2010207234A (ja) | 2010-09-24 |
| JP2005520519A (ja) | 2005-07-14 |
| US20060078552A1 (en) | 2006-04-13 |
| AU2003215869B2 (en) | 2008-04-24 |
| DE60316124T3 (de) | 2018-03-22 |
| DK1485475T3 (da) | 2008-01-21 |
| DE60316124T2 (de) | 2008-06-05 |
| ATE372379T1 (de) | 2007-09-15 |
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