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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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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| 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 |
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| CA2479153A1 CA2479153A1 (en) | 2003-09-25 |
| CA2479153C true CA2479153C (en) | 2015-06-02 |
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| WO (1) | WO2003078619A1 (enExample) |
Families Citing this family (159)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003078619A1 (en) | 2002-03-15 | 2003-09-25 | 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 |
| US20100151556A1 (en) * | 2002-03-15 | 2010-06-17 | Cellectis | Hybrid and single chain meganucleases and use thereof |
| EP1590468A2 (en) * | 2003-01-28 | 2005-11-02 | Cellectis | Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof |
| EP1591521A1 (en) * | 2004-04-30 | 2005-11-02 | Cellectis | I-Dmo I derivatives with enhanced activity at 37 degrees C and use thereof |
| WO2006097854A1 (en) | 2005-03-15 | 2006-09-21 | Cellectis | Heterodimeric meganucleases and use thereof |
| WO2007034262A1 (en) * | 2005-09-19 | 2007-03-29 | Cellectis | Heterodimeric meganucleases and use thereof |
| WO2007014275A2 (en) * | 2005-07-26 | 2007-02-01 | Sangamo Biosciences, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
| ES2626025T3 (es) | 2005-10-18 | 2017-07-21 | 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 |
| EP2602323B1 (en) | 2007-06-01 | 2018-02-28 | Open Monoclonal Technology, Inc. | Compositions and methods for inhibiting endogenous immunoglobin genes and producing transgenic human idiotype antibodies |
| US20140112904A9 (en) | 2007-06-06 | 2014-04-24 | Cellectis | Method for enhancing the cleavage activity of i-crei derived meganucleases |
| WO2008149176A1 (en) * | 2007-06-06 | 2008-12-11 | Cellectis | Meganuclease variants cleaving a dna target sequence from the mouse rosa26 locus and uses thereof |
| WO2009006297A2 (en) | 2007-06-29 | 2009-01-08 | 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 |
| US8563314B2 (en) | 2007-09-27 | 2013-10-22 | Sangamo Biosciences, 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 |
| US20110014616A1 (en) * | 2009-06-30 | 2011-01-20 | Sangamo Biosciences, Inc. | Rapid screening of biologically active nucleases and isolation of nuclease-modified cells |
| US11235026B2 (en) | 2007-09-27 | 2022-02-01 | Sangamo Therapeutics, Inc. | Methods and compositions for modulating PD1 |
| AU2015201270B2 (en) * | 2007-10-31 | 2017-01-19 | Precision Biosciences, Inc. | Rationally-designed single-chain meganucleases with non-palindromic recognition sequences |
| EP2660317B1 (en) * | 2007-10-31 | 2016-04-06 | Precision Biosciences, Inc. | Rationally-designed single-chain meganucleases with non-palindromic recognition sequences |
| AU2008335324A1 (en) * | 2007-12-07 | 2009-06-18 | Precision Biosciences, Inc. | Rationally-designed meganucleases with recognition sequences found in DNase hypersensitive regions of the human genome |
| 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 |
| JP2011519558A (ja) * | 2008-04-28 | 2011-07-14 | プレシジョン バイオサイエンシズ，インク． | 合理的に設計されたｄｎａ結合タンパク質とエフェクタードメインとの融合分子 |
| DK2313498T3 (en) | 2008-07-14 | 2017-05-22 | Prec Biosciences Inc | RECOGNITION SEQUENCES FOR I-CREI-DERIVED MECHANUCLEASES AND APPLICATIONS 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 |
| US20110294217A1 (en) * | 2009-02-12 | 2011-12-01 | Fred Hutchinson Cancer Research Center | Dna nicking enzyme from a homing endonuclease that stimulates site-specific gene conversion |
| CA2755192C (en) | 2009-03-20 | 2018-09-11 | 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 |
| 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 |
| KR20170125406A (ko) | 2009-08-11 | 2017-11-14 | 상가모 테라퓨틱스, 인코포레이티드 | 표적화 변형에 대한 동형접합성 유기체 |
| 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 |
| WO2011036640A2 (en) | 2009-09-24 | 2011-03-31 | Cellectis | Meganuclease reagents of uses thereof for treating genetic diseases caused by frame shift/non sense mutations |
| 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 |
| US10316304B2 (en) | 2009-11-27 | 2019-06-11 | Basf Plant Science Company Gmbh | Chimeric endonucleases and uses thereof |
| AU2010339481B2 (en) | 2009-12-30 | 2016-02-04 | 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 |
| CN103097527A (zh) * | 2010-02-26 | 2013-05-08 | 塞勒克提斯公司 | 用于将转基因插入安全港座位的内切核酸酶的用途 |
| CN103025866A (zh) | 2010-03-22 | 2013-04-03 | 菲利普莫里斯生产公司 | 修饰植物中酶的活性 |
| WO2011141825A1 (en) | 2010-05-12 | 2011-11-17 | Cellectis | Meganuclease variants cleaving a dna target sequence from the rhodopsin gene and uses thereof |
| US20130145487A1 (en) | 2010-05-12 | 2013-06-06 | Cellectis | Meganuclease variants cleaving a dna target sequence from the dystrophin gene and uses thereof |
| CA2798988C (en) | 2010-05-17 | 2020-03-10 | Sangamo Biosciences, Inc. | Tal-effector (tale) dna-binding polypeptides and uses thereof |
| CA2802822A1 (en) | 2010-06-15 | 2012-01-05 | Cellectis | Method for improving cleavage of dna by endonuclease sensitive to methylation |
| SG186932A1 (en) | 2010-07-07 | 2013-02-28 | 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 |
| CA2807270A1 (en) | 2010-08-02 | 2012-02-09 | Cellectis | Method for targeted genomic events in diatoms |
| JP2013544082A (ja) | 2010-10-27 | 2013-12-12 | セレクティス | 二本鎖破断−誘導変異誘発の効率を増大させる方法 |
| US9044492B2 (en) | 2011-02-04 | 2015-06-02 | Cellectis Sa | Method for modulating the efficiency of double-strand break-induced mutagenesis |
| BR112013024337A2 (pt) | 2011-03-23 | 2017-09-26 | Du Pont | locus de traço transgênico complexo em uma planta, planta ou semente, método para produzir em uma planta um locus de traço transgênico complexo e construto de expressão |
| WO2012138901A1 (en) | 2011-04-05 | 2012-10-11 | Cellectis Sa | Method for enhancing rare-cutting endonuclease efficiency and uses thereof |
| EP2694091B1 (en) | 2011-04-05 | 2019-03-13 | Cellectis | Method for the generation of compact tale-nucleases and uses thereof |
| PT2702160T (pt) | 2011-04-27 | 2020-07-30 | Amyris Inc | Métodos para modificação genómica |
| 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 |
| CN103620027B (zh) | 2011-06-10 | 2017-11-21 | 巴斯夫植物科学有限公司 | 核酸酶融合蛋白及其用途 |
| MX2013015174A (es) | 2011-06-21 | 2014-09-22 | Pioneer Hi Bred Int | Metodos y composiciones para producir plantas esteriles masculinas. |
| 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 |
| BR112014021104B1 (pt) | 2012-02-29 | 2023-03-28 | Sangamo Biosciences, Inc | Proteína de fusão de ocorrência não natural compreendendo um domínio de ligação de dna de dedo de zinco manipulado que se liga a um gene htt, seu uso, método in vitro de modificação da expressão de um gene htt em uma célula, e método de geração de um sistema modelo para o estudo da doença de huntington |
| CN104411823A (zh) | 2012-05-04 | 2015-03-11 | 纳幕尔杜邦公司 | 包含具有大范围核酸酶活性的序列的组合物和方法 |
| WO2014018601A2 (en) | 2012-07-24 | 2014-01-30 | Cellectis | New modular base-specific nucleic acid binding domains from burkholderia rhizoxinica proteins |
| ES2824024T3 (es) | 2012-10-10 | 2021-05-11 | Sangamo Therapeutics Inc | Compuestos modificadores de células T y usos de los mismos |
| AU2013346504A1 (en) | 2012-11-16 | 2015-06-18 | Cellectis | Method for targeted modification of algae genomes |
| WO2014102688A1 (en) | 2012-12-27 | 2014-07-03 | Cellectis | New design matrix for improvement of homology-directed gene targeting |
| JP6475172B2 (ja) | 2013-02-20 | 2019-02-27 | 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． | ラットの遺伝子組換え |
| US10329574B2 (en) | 2013-03-12 | 2019-06-25 | E I Du Pont De Nemours And Company | Methods for the identification of variant recognition sites for rare-cutting engineered double-strand-break-inducing agents and compositions and uses thereof |
| JP6873530B2 (ja) * | 2013-03-15 | 2021-05-19 | イン3バイオ・リミテッドIn3Bio Ltd. | 自己組織化合成タンパク質（Ｓｅｌｆ−Ａｓｓｅｍｂｌｉｎｇ Ｓｙｎｔｈｅｔｉｃ Ｐｒｏｔｅｉｎｓ） |
| EP3456831B1 (en) | 2013-04-16 | 2021-07-14 | Regeneron Pharmaceuticals, Inc. | Targeted modification of rat genome |
| CN105934524A (zh) | 2013-11-11 | 2016-09-07 | 桑格摩生物科学股份有限公司 | 用于治疗亨廷顿氏病的方法和组合物 |
| ES2975317T3 (es) | 2013-12-11 | 2024-07-04 | Regeneron Pharma | Métodos y composiciones para la modificación dirigida de un genoma |
| MX388127B (es) | 2013-12-11 | 2025-03-19 | Regeneron Pharma | Metodos y composiciones para la modificacion dirigida de un genoma. |
| AU2014368982B2 (en) | 2013-12-19 | 2021-03-25 | Amyris, Inc. | Methods for genomic integration |
| HRP20201906T1 (hr) | 2013-12-20 | 2021-04-02 | Fred Hutchinson Cancer Research Center | Označene kimerne efektorske molekule i njihovi receptori |
| AU2015231353B2 (en) | 2014-03-18 | 2020-11-05 | Sangamo Therapeutics, Inc. | Methods and compositions for regulation of zinc finger protein expression |
| BR112016028564A2 (pt) | 2014-06-06 | 2018-01-30 | Regeneron Pharma | método para modificar um locus-alvo em uma célula. |
| MX384887B (es) | 2014-06-23 | 2025-03-14 | Regeneron Pharma | Ensamblaje de adn mediado por nucleasa. |
| SG10201911411YA (en) | 2014-06-26 | 2020-02-27 | Regeneron Pharma | Methods and compositions for targeted genetic modifications and methods of use |
| CA2963315A1 (en) | 2014-10-15 | 2016-04-21 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for generating or maintaining pluripotent cells |
| BR112017013104A2 (pt) | 2014-12-19 | 2018-05-15 | Regeneron Pharma | métodos para modificar um locus genômico alvo em uma célula, para intensificar a recombinação homóloga em um locus genômico alvo em uma célula e para produzir uma geração f0 de um animal não humano. |
| EP4335918A3 (en) | 2015-04-03 | 2024-04-17 | Dana-Farber Cancer Institute, Inc. | Composition and methods of genome editing of b-cells |
| WO2016176652A2 (en) | 2015-04-29 | 2016-11-03 | Fred Hutchinson Cancer Research Center | Modified stem cells and uses thereof |
| ES2983043T3 (es) | 2015-12-18 | 2024-10-21 | Sangamo Therapeutics Inc | Alteración dirigida del receptor de células T |
| CN108699132B (zh) | 2015-12-18 | 2023-08-11 | 桑格摩生物治疗股份有限公司 | Mhc细胞受体的靶向破坏 |
| US11293033B2 (en) | 2016-05-18 | 2022-04-05 | Amyris, Inc. | Compositions and methods for genomic integration of nucleic acids into exogenous landing pads |
| BR112019001783A2 (pt) | 2016-07-29 | 2019-05-07 | Regeneron Pharmaceuticals, Inc. | mamífero não humano, e, métodos para produzir o mamífero não humano e de triagem de um composto. |
| US10975393B2 (en) | 2016-08-24 | 2021-04-13 | Sangamo Therapeutics, Inc. | Engineered target specific nucleases |
| WO2018058002A1 (en) | 2016-09-23 | 2018-03-29 | Fred Hutchinson Cancer Research Center | Tcrs specific for minor histocompatibility (h) antigen ha-1 and uses thereof |
| SG10202109874VA (en) | 2017-01-19 | 2021-10-28 | Open Monoclonal Tech Inc | Human antibodies from transgenic rodents with multiple heavy chain immunoglobulin loci |
| BR112019018863A8 (pt) | 2017-03-15 | 2023-05-02 | Hutchinson Fred Cancer Res | Tcrs de alta afinidade específicos para mage-a1 e usos dos mesmos |
| US11820728B2 (en) | 2017-04-28 | 2023-11-21 | Acuitas Therapeutics, Inc. | Carbonyl lipids and lipid nanoparticle formulations for delivery of nucleic acids |
| CN110869497A (zh) | 2017-05-03 | 2020-03-06 | 桑格摩生物治疗股份有限公司 | 修饰囊性纤维化跨膜传导调节蛋白（cftr）基因的方法和组合物 |
| US10780119B2 (en) | 2017-05-24 | 2020-09-22 | Effector Therapeutics Inc. | Methods and compositions for cellular immunotherapy |
| MX2020001287A (es) | 2017-08-11 | 2020-08-20 | Hutchinson Fred Cancer Res | Receptor de linfocitos t (tcrs) especificos de braf y usos de los mismos. |
| LT3675623T (lt) | 2017-08-29 | 2025-09-10 | KWS SAAT SE & Co. KGaA | Patobulintas mėlynasis aleuronas ir kitos segregacijos sistemos |
| CN111065410A (zh) | 2017-09-06 | 2020-04-24 | 弗雷德哈钦森癌症研究中心 | 用于改善过继细胞疗法的方法 |
| WO2019051128A1 (en) | 2017-09-06 | 2019-03-14 | Fred Hutchinson Cancer Research Center | SPECIFIC STREP LABEL CHIMERIC RECEPTORS AND USES THEREOF |
| EP3585162B1 (en) | 2017-09-29 | 2023-08-30 | Regeneron Pharmaceuticals, Inc. | Rodents comprising a humanized ttr locus and methods of use |
| EP3697435A1 (en) | 2017-10-20 | 2020-08-26 | Fred Hutchinson Cancer Research Center | Compositions and methods of immunotherapy targeting tigit and/or cd112r or comprising cd226 overexpression |
| WO2019109047A1 (en) | 2017-12-01 | 2019-06-06 | 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 |
| CA3091138A1 (en) | 2018-02-26 | 2019-08-29 | Fred Hutchinson Cancer Research Center | Compositions and methods for cellular immunotherapy |
| AU2019234474B2 (en) | 2018-03-12 | 2025-05-15 | Pioneer Hi-Bred International, Inc. | Methods for plant transformation |
| 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 |
| JP2021534752A (ja) | 2018-08-22 | 2021-12-16 | フレッド ハッチンソン キャンサー リサーチ センター | Ｋｒａｓ抗原またはｈｅｒ２抗原を標的とする免疫療法 |
| WO2020047099A1 (en) | 2018-08-28 | 2020-03-05 | Fred Hutchinson Cancer Research Center | Methods and compositions for adoptive t cell therapy incorporating induced notch signaling |
| WO2020061161A1 (en) | 2018-09-18 | 2020-03-26 | Sangamo Therapeutics, Inc. | Programmed cell death 1 (pd1) specific nucleases |
| EP3852911B1 (en) | 2018-09-21 | 2025-01-22 | Acuitas Therapeutics, Inc. | Systems and methods for manufacturing lipid nanoparticles and liposomes |
| WO2020068702A1 (en) | 2018-09-24 | 2020-04-02 | Fred Hutchinson Cancer Research Center | Chimeric receptor proteins and uses thereof |
| WO2020097530A2 (en) | 2018-11-09 | 2020-05-14 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting mesothelin |
| KR20200071198A (ko) | 2018-12-10 | 2020-06-19 | 네오이뮨텍, 인코퍼레이티드 | Nrf2 발현 조절 기반 T 세포 항암면역치료법 |
| KR20210105914A (ko) | 2018-12-20 | 2021-08-27 | 리제너론 파마슈티칼스 인코포레이티드 | 뉴클레아제-매개 반복부 팽창 |
| US11453639B2 (en) | 2019-01-11 | 2022-09-27 | Acuitas Therapeutics, Inc. | Lipids for lipid nanoparticle delivery of active agents |
| GB2596461B (en) | 2019-02-20 | 2023-09-27 | Fred Hutchinson Cancer Center | Binding proteins specific for RAS neoantigens and uses thereof |
| US12448430B2 (en) | 2019-03-11 | 2025-10-21 | Fred Hutchinson Cancer Center | High avidity WT1 T cell receptors and uses thereof |
| ES2923629T3 (es) | 2019-04-04 | 2022-09-29 | Regeneron Pharma | Métodos para la introducción sin cicatrices de modificaciones dirigidas en vectores de direccionamiento |
| AU2020253532B2 (en) | 2019-04-04 | 2024-06-20 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized coagulation factor 12 locus |
| WO2020247452A1 (en) | 2019-06-04 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use |
| SG11202111256XA (en) | 2019-06-07 | 2021-11-29 | Regeneron Pharma | Non-human animals comprising a humanized albumin locus |
| EP4017872A1 (en) | 2019-08-20 | 2022-06-29 | Fred Hutchinson Cancer Center | T-cell immunotherapy specific for wt-1 |
| WO2021108363A1 (en) | 2019-11-25 | 2021-06-03 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-mediated upregulation of humanized ttr allele |
| MX2023000614A (es) | 2020-07-16 | 2023-02-13 | Acuitas Therapeutics Inc | Lipidos cationicos para usarse en nanoparticulas lipidicas. |
| US12152251B2 (en) | 2020-08-25 | 2024-11-26 | Kite Pharma, Inc. | T cells with improved functionality |
| WO2022066965A2 (en) | 2020-09-24 | 2022-03-31 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting sox2 antigens |
| WO2022066973A1 (en) | 2020-09-24 | 2022-03-31 | Fred Hutchinson Cancer Research Center | Immunotherapy targeting pbk or oip5 antigens |
| TW202222841A (zh) | 2020-10-06 | 2022-06-16 | 福瑞德哈金森腫瘤研究中心 | 用於治療表現mage-a1之疾病的組成物及方法 |
| 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 |
| JP2024520676A (ja) | 2021-06-02 | 2024-05-24 | ライエル・イミュノファーマ・インコーポレイテッド | Ｎｒ４ａ３欠損免疫細胞及びその使用 |
| WO2023288281A2 (en) | 2021-07-15 | 2023-01-19 | Fred Hutchinson Cancer Center | Chimeric polypeptides |
| WO2023014922A1 (en) | 2021-08-04 | 2023-02-09 | The Regents Of The University Of Colorado, A Body Corporate | Lat activating chimeric antigen receptor t cells and methods of use thereof |
| CN118119702A (zh) | 2021-10-14 | 2024-05-31 | 隆萨销售股份有限公司 | 用于细胞外囊泡产生的经修饰的生产者细胞 |
| WO2023081756A1 (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 |
| IL313486A (en) | 2021-12-16 | 2024-08-01 | Acuitas Therapeutics Inc | Lipids for use in lipid nanoparticle formulations |
| EP4457342A1 (en) | 2021-12-29 | 2024-11-06 | 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 |
| CA3256953A1 (en) | 2022-05-09 | 2023-11-16 | Regeneron Pharma | VECTORS AND METHODS FOR IN VIVO ANTIBODY PRODUCTION |
| EP4525892A1 (en) | 2022-05-19 | 2025-03-26 | Lyell Immunopharma, Inc. | Polynucleotides targeting nr4a3 and uses thereof |
| 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 |
| US5641670A (en) * | 1991-11-05 | 1997-06-24 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| 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 |
| 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 |
| US5792632A (en) * | 1992-05-05 | 1998-08-11 | Institut Pasteur | Nucleotide sequence encoding the enzyme I-SceI and the uses thereof |
| US5474896A (en) | 1992-05-05 | 1995-12-12 | 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 |
| ATE513037T1 (de) | 1993-02-12 | 2011-07-15 | Univ Johns Hopkins | Funktionelle domänen der restriktionsendonukleasen aus flavobakterium okeanokoites (foki) |
| 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 |
| WO2000046386A2 (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 |
| CA2360878A1 (en) | 1999-02-03 | 2000-08-10 | The Children's Medical Center Corporation | Gene repair involving excision of targeting dna |
| AU2001297625A1 (en) * | 2000-12-21 | 2002-09-12 | 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 |
| AU2002353934A1 (en) * | 2001-10-31 | 2003-05-12 | Oxford Glycosciences (Uk) Ltd. | Biomarkers of liver function |
| US7462758B2 (en) * | 2001-12-20 | 2008-12-09 | Sungene Gmbh & Co. Kgaa | Methods for the transformation of vegetal plastids |
| WO2009095742A1 (en) † | 2008-01-31 | 2009-08-06 | Cellectis | New i-crei derived single-chain meganuclease and uses thereof |
| WO2003078619A1 (en) | 2002-03-15 | 2003-09-25 | Cellectis | Hybrid and single chain meganucleases and use thereof |
| EP1590468A2 (en) * | 2003-01-28 | 2005-11-02 | Cellectis | Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application 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 |
| ES2626025T3 (es) † | 2005-10-18 | 2017-07-21 | Precision Biosciences | Meganucleasas diseñadas racionalmente con especificidad de secuencia y afinidad de unión a ADN alteradas |
| WO2009006297A2 (en) † | 2007-06-29 | 2009-01-08 | Pioneer Hi-Bred International, Inc. | Methods for altering the genome of a monocot plant cell |
| EP2660317B1 (en) † | 2007-10-31 | 2016-04-06 | 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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| US20060078552A1 (en) | 2006-04-13 |
| JP2005520519A (ja) | 2005-07-14 |
| US8206965B2 (en) | 2012-06-26 |
| AU2003215869B2 (en) | 2008-04-24 |
| DK1485475T3 (da) | 2008-01-21 |
| JP2010207234A (ja) | 2010-09-24 |
| CA2479153A1 (en) | 2003-09-25 |
| DE60316124D1 (de) | 2007-10-18 |
| DE60316124T3 (de) | 2018-03-22 |
| DE60316124T2 (de) | 2008-06-05 |
| EP1485475A1 (en) | 2004-12-15 |
| JP2011188867A (ja) | 2011-09-29 |
| ATE372379T1 (de) | 2007-09-15 |
| ES2292994T3 (es) | 2008-03-16 |
| EP1485475B1 (en) | 2007-09-05 |
| EP1485475B2 (en) | 2017-09-20 |
| US20040002092A1 (en) | 2004-01-01 |
| AU2003215869A1 (en) | 2003-09-29 |
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