CA2910427C - Delivery methods and compositions for nuclease-mediated genome engineering - Google Patents
Delivery methods and compositions for nuclease-mediated genome engineering Download PDFInfo
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- CA2910427C CA2910427C CA2910427A CA2910427A CA2910427C CA 2910427 C CA2910427 C CA 2910427C CA 2910427 A CA2910427 A CA 2910427A CA 2910427 A CA2910427 A CA 2910427A CA 2910427 C CA2910427 C CA 2910427C
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- A01K2207/12—Animals modified by administration of exogenous cells
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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| PCT/US2014/036972 WO2014182700A1 (en) | 2013-05-10 | 2014-05-06 | Delivery methods and compositions for nuclease-mediated genome engineering |
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| AU2013355214B2 (en) | 2012-12-06 | 2017-06-15 | Sigma-Aldrich Co. Llc | Crispr-based genome modification and regulation |
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| WO2014204578A1 (en) | 2013-06-21 | 2014-12-24 | The General Hospital Corporation | Using rna-guided foki nucleases (rfns) to increase specificity for rna-guided genome editing |
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| US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
| WO2015040402A1 (en) | 2013-09-18 | 2015-03-26 | Kymab Limited | Methods. cells & organisms |
| PT3066201T (pt) | 2013-11-07 | 2018-06-04 | Massachusetts Inst Technology | Métodos e composições relacionadas com crispr com arng reguladores |
| RU2725520C2 (ru) | 2013-12-11 | 2020-07-02 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для направленной модификации генома |
| US9068179B1 (en) | 2013-12-12 | 2015-06-30 | President And Fellows Of Harvard College | Methods for correcting presenilin point mutations |
| WO2015165275A1 (zh) * | 2014-04-30 | 2015-11-05 | 清华大学 | 利用tale转录抑制子在哺乳动物细胞中模块化构建合成基因线路 |
| WO2015165276A1 (zh) * | 2014-04-30 | 2015-11-05 | 清华大学 | 利用tale转录抑制子在哺乳动物细胞中模块化构建合成基因线路的试剂盒 |
| WO2015188065A1 (en) | 2014-06-05 | 2015-12-10 | Sangamo Biosciences, Inc. | Methods and compositions for nuclease design |
| WO2015200378A1 (en) | 2014-06-23 | 2015-12-30 | The General Hospital Corporation | Genomewide unbiased identification of dsbs evaluated by sequencing (guide-seq) |
| US9816074B2 (en) | 2014-07-25 | 2017-11-14 | Sangamo Therapeutics, Inc. | Methods and compositions for modulating nuclease-mediated genome engineering in hematopoietic stem cells |
| US9757420B2 (en) | 2014-07-25 | 2017-09-12 | Sangamo Therapeutics, Inc. | Gene editing for HIV gene therapy |
| US10077453B2 (en) | 2014-07-30 | 2018-09-18 | President And Fellows Of Harvard College | CAS9 proteins including ligand-dependent inteins |
| US9616090B2 (en) | 2014-07-30 | 2017-04-11 | Sangamo Biosciences, Inc. | Gene correction of SCID-related genes in hematopoietic stem and progenitor cells |
| IL301900A (en) | 2014-11-21 | 2023-06-01 | Regeneron Pharma | Methods and compositions for targeted genetic modification using paired guide rnas |
| EP3245232B1 (en) | 2015-01-12 | 2021-04-21 | The Regents of The University of California | Heterodimeric cas9 and methods of use thereof |
| US11180792B2 (en) | 2015-01-28 | 2021-11-23 | The Regents Of The University Of California | Methods and compositions for labeling a single-stranded target nucleic acid |
| US9944912B2 (en) | 2015-03-03 | 2018-04-17 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases with altered PAM specificity |
| JP2018513681A (ja) * | 2015-03-31 | 2018-05-31 | エクセリゲン サイエンティフィック, インコーポレイテッドExeligen Scientific, Inc. | 細胞または生物のゲノムへのＤＮＡ配列の標的化組み込みのためのＣａｓ９レトロウイルスインテグラーゼおよびＣａｓ９レコンビナーゼ系 |
| WO2016196655A1 (en) | 2015-06-03 | 2016-12-08 | The Regents Of The University Of California | Cas9 variants and methods of use thereof |
| KR102668608B1 (ko) | 2015-08-28 | 2024-05-24 | 더 제너럴 하스피탈 코포레이션 | 조작된 crispr-cas9 뉴클레아제 |
| US9512446B1 (en) | 2015-08-28 | 2016-12-06 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| US9926546B2 (en) | 2015-08-28 | 2018-03-27 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| WO2017044843A1 (en) | 2015-09-11 | 2017-03-16 | The General Hospital Corporation | Full interrogation of nuclease dsbs and sequencing (find-seq) |
| WO2017053729A1 (en) | 2015-09-25 | 2017-03-30 | The Board Of Trustees Of The Leland Stanford Junior University | Nuclease-mediated genome editing of primary cells and enrichment thereof |
| AU2016331185A1 (en) | 2015-09-30 | 2018-04-26 | The General Hospital Corporation | Comprehensive in vitro reporting of cleavage events by sequencing (CIRCLE-seq) |
| EP3365356B1 (en) | 2015-10-23 | 2023-06-28 | President and Fellows of Harvard College | Nucleobase editors and uses thereof |
| ES2895430T3 (es) | 2016-01-15 | 2022-02-21 | Univ Minnesota | Métodos y composiciones para el tratamiento de enfermedad neurológica |
| JP7012650B2 (ja) | 2016-02-02 | 2022-01-28 | サンガモ セラピューティクス， インコーポレイテッド | Ｄｎａ結合ドメインと切断ドメインとを連結するための組成物 |
| US20190249172A1 (en) | 2016-02-18 | 2019-08-15 | The Regents Of The University Of California | Methods and compositions for gene editing in stem cells |
| JP2019515654A (ja) | 2016-03-16 | 2019-06-13 | ザ ジェイ． デヴィッド グラッドストーン インスティテューツ | 肥満及び／又は糖尿病を処置するための方法及び組成物、並びに候補処置薬剤を識別するための方法及び組成物 |
| JP7324583B2 (ja) | 2016-05-20 | 2023-08-10 | 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 | 複数のガイドｒｎａを使用して免疫寛容を破綻させるための方法 |
| CN109803530A (zh) | 2016-07-29 | 2019-05-24 | 瑞泽恩制药公司 | 包含引起c-截短的原纤维蛋白-1表达的突变的小鼠 |
| JP7231935B2 (ja) | 2016-08-03 | 2023-03-08 | プレジデント アンド フェローズ オブ ハーバード カレッジ | アデノシン核酸塩基編集因子およびそれらの使用 |
| EP3497214B1 (en) | 2016-08-09 | 2023-06-28 | President and Fellows of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| WO2018064371A1 (en) | 2016-09-30 | 2018-04-05 | The Regents Of The University Of California | Rna-guided nucleic acid modifying enzymes and methods of use thereof |
| US10669539B2 (en) | 2016-10-06 | 2020-06-02 | Pioneer Biolabs, Llc | Methods and compositions for generating CRISPR guide RNA libraries |
| EP3526320A1 (en) | 2016-10-14 | 2019-08-21 | President and Fellows of Harvard College | Aav delivery of nucleobase editors |
| EP4667565A2 (en) | 2016-10-20 | 2025-12-24 | Sangamo Therapeutics, Inc. | Methods and compositions for the treatment of fabry disease |
| WO2018081775A1 (en) | 2016-10-31 | 2018-05-03 | Sangamo Therapeutics, Inc. | Gene correction of scid-related genes in hematopoietic stem and progenitor cells |
| EP3535400A4 (en) * | 2016-11-02 | 2020-07-01 | David Kiewlich | PLASMIDIC VECTORS FOR EXPRESSION OF LARGE NUCLEIC ACID TRANSGENES |
| KR20210035022A (ko) | 2016-12-14 | 2021-03-31 | 리간달 인코포레이티드 | 핵산 및/또는 단백질 적재물 전달을 위한 조성물 및 방법 |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| JP2020505037A (ja) | 2017-01-19 | 2020-02-20 | オープン モノクローナル テクノロジー，インコーポレイテッド | 複数の重鎖免疫グロブリン遺伝子座を有するトランスジェニックげっ歯類由来のヒト抗体 |
| SG11201906735RA (en) | 2017-01-23 | 2019-08-27 | Regeneron Pharma | Hydroxysteroid 17-beta dehydrogenase 13 (hsd17b13) variants and uses thereof |
| US20190365818A1 (en) * | 2017-02-09 | 2019-12-05 | Allen Institute | Genetically-tagged stem cell lines and methods of use |
| WO2018165631A1 (en) | 2017-03-09 | 2018-09-13 | President And Fellows Of Harvard College | Cancer vaccine |
| WO2018165504A1 (en) | 2017-03-09 | 2018-09-13 | President And Fellows Of Harvard College | Suppression of pain by gene editing |
| KR20190127797A (ko) | 2017-03-10 | 2019-11-13 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 시토신에서 구아닌으로의 염기 편집제 |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
| EP3612551B1 (en) | 2017-04-21 | 2024-09-04 | The General Hospital Corporation | Variants of cpf1 (cas12a) with altered pam specificity |
| US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
| US11326157B2 (en) | 2017-05-25 | 2022-05-10 | The General Hospital Corporation | Base editors with improved precision and specificity |
| WO2019023680A1 (en) | 2017-07-28 | 2019-01-31 | President And Fellows Of Harvard College | METHODS AND COMPOSITIONS FOR EVOLUTION OF BASIC EDITORS USING PHAGE-ASSISTED CONTINUOUS EVOLUTION (PACE) |
| CA3073448A1 (en) | 2017-08-23 | 2019-02-28 | The General Hospital Corporation | Engineered crispr-cas9 nucleases with altered pam specificity |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| WO2019075197A1 (en) | 2017-10-11 | 2019-04-18 | The General Hospital Corporation | METHODS OF DETECTION OF INDIVIDUAL SITE-SPECIFIC PARASITE GENOMIC DEAMINATION BY BASE EDITING TECHNOLOGIES |
| CN111757937A (zh) | 2017-10-16 | 2020-10-09 | 布罗德研究所股份有限公司 | 腺苷碱基编辑器的用途 |
| JP2021502085A (ja) | 2017-11-09 | 2021-01-28 | サンガモ セラピューティクス， インコーポレイテッド | サイトカイン誘導性ｓｈ２含有タンパク質（ｃｉｓｈ）遺伝子の遺伝子改変 |
| US20220290186A1 (en) * | 2017-12-06 | 2022-09-15 | Generation Bio Co. | Gene editing using a modified closed-ended dna (cedna) |
| WO2019118949A1 (en) | 2017-12-15 | 2019-06-20 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| WO2019157239A1 (en) * | 2018-02-08 | 2019-08-15 | David Kiewlich | Plasmid vectors for expression of large nucleic acid transgenes |
| CA3092088A1 (en) * | 2018-03-15 | 2019-09-19 | Igtx, Llc | Synthetic dna vectors and methods of use |
| CA3097044A1 (en) | 2018-04-17 | 2019-10-24 | The General Hospital Corporation | Sensitive in vitro assays for substrate preferences and sites of nucleic acid binding, modifying, and cleaving agents |
| CN112313246B (zh) | 2018-04-18 | 2025-05-13 | 桑格摩生物治疗股份有限公司 | 用于调节亨廷顿蛋白(htt)的锌指蛋白组合物 |
| US12378565B2 (en) | 2018-05-07 | 2025-08-05 | Pioneer Hi-Bred International, Inc. | Methods and compositions for homology directed repair of double strand breaks in plant cell genomes |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| WO2020014528A1 (en) | 2018-07-13 | 2020-01-16 | The Regents Of The University Of California | Retrotransposon-based delivery vehicle and methods of use thereof |
| WO2020041456A1 (en) | 2018-08-22 | 2020-02-27 | The Regents Of The University Of California | Variant type v crispr/cas effector polypeptides and methods of use thereof |
| MX2021004277A (es) | 2018-10-18 | 2021-09-08 | Intellia Therapeutics Inc | Composiciones y metodos para expresar el factor ix. |
| US11407995B1 (en) | 2018-10-26 | 2022-08-09 | Inari Agriculture Technology, Inc. | RNA-guided nucleases and DNA binding proteins |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| US11434477B1 (en) | 2018-11-02 | 2022-09-06 | Inari Agriculture Technology, Inc. | RNA-guided nucleases and DNA binding proteins |
| EP3877517A4 (en) | 2018-11-09 | 2022-09-07 | Inari Agriculture, Inc. | RNA-DRIVEN NUCLEASES AND DNA-BINDING PROTEINS |
| WO2020154500A1 (en) | 2019-01-23 | 2020-07-30 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| EP3921417A4 (en) | 2019-02-04 | 2022-11-09 | The General Hospital Corporation | VARIANTS OF ADENINE DNA BASES WITH REDUCED OFF-TARGET RNA EDIT |
| AU2019428629A1 (en) | 2019-02-06 | 2021-01-28 | Sangamo Therapeutics, Inc. | Method for the treatment of mucopolysaccharidosis type I |
| US12460230B2 (en) | 2019-02-10 | 2025-11-04 | The J. David Gladstone Institutes | Modified mitochondrion and methods of use thereof |
| MX2021010559A (es) | 2019-03-07 | 2021-12-15 | Univ California | Polipéptidos efectores de crispr-cas y métodos de uso de estos. |
| MX2021011426A (es) | 2019-03-19 | 2022-03-11 | Broad Inst Inc | Metodos y composiciones para editar secuencias de nucleótidos. |
| WO2020205889A1 (en) | 2019-04-01 | 2020-10-08 | Tenaya Therapeutics, Inc. | Adeno-associated virus with engineered capsid |
| EP3956349A1 (en) | 2019-04-17 | 2022-02-23 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| CA3137896A1 (en) * | 2019-04-24 | 2020-10-29 | Seattle Children's Hospital D/B/A Seattle Children's Research Institute | Wiskott-aldrich syndrome gene homing endonuclease variants, compositions, and methods of use |
| US11622547B2 (en) | 2019-06-07 | 2023-04-11 | Regeneran Pharmaceuticals, Inc. | Genetically modified mouse that expresses human albumin |
| JP2022539346A (ja) * | 2019-06-26 | 2022-09-08 | ビロベク，インコーポレイテッド | バキュロウイルス発現系 |
| US12457951B2 (en) | 2019-08-14 | 2025-11-04 | Pairwise Plants Services, Inc. | Alteration of flavor traits in consumer crops via disablement of the myrosinase/glucosinolate system |
| GB2606844B (en) | 2019-09-18 | 2025-08-06 | Aldevron Llc | Synthetic DNA vectors and methods of use |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| EP4093864A4 (en) | 2020-01-24 | 2024-04-10 | The General Hospital Corporation | Unconstrained genome targeting with near-pamless engineered crispr-cas9 variants |
| WO2021151085A2 (en) | 2020-01-24 | 2021-07-29 | The General Hospital Corporation | Crispr-cas enzymes with enhanced on-target activity |
| EP4097144A4 (en) * | 2020-01-28 | 2024-02-28 | University of Southern California | GENOMIC ENGINEERING OF HUMAN IMMUNOGLOBULIN LOCUS TO EXPRESS RECOMBINANT BINDING-SITE MOLECULES |
| EP4114946A1 (en) | 2020-03-04 | 2023-01-11 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for sensitization of tumor cells to immune therapy |
| MX2022014008A (es) | 2020-05-08 | 2023-02-09 | Broad Inst Inc | Métodos y composiciones para la edición simultánea de ambas cadenas de una secuencia de nucleótidos de doble cadena objetivo. |
| EP4596696A3 (en) | 2021-09-28 | 2025-08-27 | Acrigen Biosciences | Compositions and methods for nucleic acid modifications |
| EP4426832A1 (en) | 2021-11-03 | 2024-09-11 | The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone | Precise genome editing using retrons |
| US20230279442A1 (en) | 2021-12-15 | 2023-09-07 | Versitech Limited | Engineered cas9-nucleases and method of use thereof |
| WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| US12171178B2 (en) | 2022-07-18 | 2024-12-24 | Pairwise Plants Services, Inc. | Mustard green plants named ‘PWRG-1’, ‘PWRG-2,’ and ‘PWSGC’ |
| AU2023311964A1 (en) | 2022-07-18 | 2025-01-30 | Renagade Therapeutics Management Inc. | Gene editing components, systems, and methods of use |
| WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| WO2025049959A2 (en) | 2023-09-01 | 2025-03-06 | Renagade Therapeutics Management Inc. | Gene editing systems, compositions, and methods for treatment of vexas syndrome |
| WO2025081042A1 (en) | 2023-10-12 | 2025-04-17 | Renagade Therapeutics Management Inc. | Nickase-retron template-based precision editing system and methods of use |
| WO2025155753A2 (en) | 2024-01-17 | 2025-07-24 | Renagade Therapeutics Management Inc. | Improved gene editing system, guides, and methods |
| WO2025174765A1 (en) | 2024-02-12 | 2025-08-21 | Renagade Therapeutics Management Inc. | Lipid nanoparticles comprising coding rna molecules for use in gene editing and as vaccines and therapeutic agents |
Family Cites Families (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6140466A (en) | 1994-01-18 | 2000-10-31 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
| US6242568B1 (en) | 1994-01-18 | 2001-06-05 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
| DE69535829D1 (de) | 1994-08-20 | 2008-10-16 | Gendaq Ltd | Verbesserung in bezug auf bindungsproteine bei der erkennung von dna |
| GB9824544D0 (en) | 1998-11-09 | 1999-01-06 | Medical Res Council | Screening system |
| US5789538A (en) | 1995-02-03 | 1998-08-04 | Massachusetts Institute Of Technology | Zinc finger proteins with high affinity new DNA binding specificities |
| US7364894B2 (en) * | 1995-09-15 | 2008-04-29 | Centelion | Circular DNA molecule having a conditional origin of replication, process for their preparation and their use in gene therapy |
| US5925523A (en) | 1996-08-23 | 1999-07-20 | President & Fellows Of Harvard College | Intraction trap assay, reagents and uses thereof |
| GB2338237B (en) | 1997-02-18 | 2001-02-28 | Actinova Ltd | In vitro peptide or protein expression library |
| GB9703369D0 (en) | 1997-02-18 | 1997-04-09 | Lindqvist Bjorn H | Process |
| GB9710809D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| US6410248B1 (en) | 1998-01-30 | 2002-06-25 | Massachusetts Institute Of Technology | General strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites |
| AU746454B2 (en) | 1998-03-02 | 2002-05-02 | Massachusetts Institute Of Technology | Poly zinc finger proteins with improved linkers |
| US6140081A (en) | 1998-10-16 | 2000-10-31 | The Scripps Research Institute | Zinc finger binding domains for GNN |
| US7070934B2 (en) | 1999-01-12 | 2006-07-04 | Sangamo Biosciences, Inc. | Ligand-controlled regulation of endogenous gene expression |
| US7013219B2 (en) | 1999-01-12 | 2006-03-14 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US6599692B1 (en) | 1999-09-14 | 2003-07-29 | Sangamo Bioscience, Inc. | Functional genomics using zinc finger proteins |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US7030215B2 (en) | 1999-03-24 | 2006-04-18 | Sangamo Biosciences, Inc. | Position dependent recognition of GNN nucleotide triplets by zinc fingers |
| US6794136B1 (en) | 2000-11-20 | 2004-09-21 | Sangamo Biosciences, Inc. | Iterative optimization in the design of binding proteins |
| AU776576B2 (en) | 1999-12-06 | 2004-09-16 | Sangamo Biosciences, Inc. | Methods of using randomized libraries of zinc finger proteins for the identification of gene function |
| KR20020086508A (ko) | 2000-02-08 | 2002-11-18 | 상가모 바이오사이언스 인코포레이티드 | 약물 발견용 세포 |
| WO2001088197A2 (en) | 2000-05-16 | 2001-11-22 | Massachusetts Institute Of Technology | Methods and compositions for interaction trap assays |
| US7029847B2 (en) | 2000-05-16 | 2006-04-18 | Massachusetts Institute Of Technology | Methods and compositions for interaction trap assays |
| US7067317B2 (en) | 2000-12-07 | 2006-06-27 | Sangamo Biosciences, Inc. | Regulation of angiogenesis with zinc finger proteins |
| GB0108491D0 (en) | 2001-04-04 | 2001-05-23 | Gendaq Ltd | Engineering zinc fingers |
| EP1421177A4 (en) | 2001-08-20 | 2006-06-07 | Scripps Research Inst | ZINC FINGER FASTENING DOMAINS FOR CNN |
| US7262054B2 (en) | 2002-01-22 | 2007-08-28 | Sangamo Biosciences, Inc. | Zinc finger proteins for DNA binding and gene regulation in plants |
| WO2003087341A2 (en) * | 2002-01-23 | 2003-10-23 | The University Of Utah Research Foundation | Targeted chromosomal mutagenesis using zinc finger nucleases |
| EP1504092B2 (en) | 2002-03-21 | 2014-06-25 | Sangamo BioSciences, Inc. | Methods and compositions for using zinc finger endonucleases to enhance homologous recombination |
| US7361635B2 (en) | 2002-08-29 | 2008-04-22 | Sangamo Biosciences, Inc. | Simultaneous modulation of multiple genes |
| US9447434B2 (en) | 2002-09-05 | 2016-09-20 | California Institute Of Technology | Use of chimeric nucleases to stimulate gene targeting |
| US7888121B2 (en) * | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| US20070134796A1 (en) | 2005-07-26 | 2007-06-14 | Sangamo Biosciences, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
| US8409861B2 (en) | 2003-08-08 | 2013-04-02 | Sangamo Biosciences, Inc. | Targeted deletion of cellular DNA sequences |
| US7972854B2 (en) | 2004-02-05 | 2011-07-05 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| CA2562193A1 (en) | 2004-04-08 | 2005-10-27 | Sangamo Biosciences, Inc. | Treatment of neuropathic pain with zinc finger proteins |
| CA2579677A1 (en) | 2004-09-16 | 2006-03-30 | Sangamo Biosciences, Inc. | Compositions and methods for protein production |
| EP1877583A2 (en) | 2005-05-05 | 2008-01-16 | Arizona Board of Regents on behalf of the Unversity of Arizona | Sequence enabled reassembly (seer) - a novel method for visualizing specific dna sequences |
| EP2027262B1 (en) | 2006-05-25 | 2010-03-31 | Sangamo Biosciences Inc. | Variant foki cleavage half-domains |
| JP5551432B2 (ja) * | 2006-05-25 | 2014-07-16 | サンガモ バイオサイエンシーズ， インコーポレイテッド | 遺伝子不活性化のための方法と組成物 |
| EP2089427B1 (en) * | 2006-11-13 | 2014-07-30 | Sangamo BioSciences, Inc. | Zinc finger nuclease for targeting the human glucocorticoid receptor locus |
| DE602008003684D1 (de) * | 2007-04-26 | 2011-01-05 | Sangamo Biosciences Inc | Gezielte integration in die ppp1r12c-position |
| EP2188384B1 (en) | 2007-09-27 | 2015-07-15 | Sangamo BioSciences, Inc. | Rapid in vivo identification of biologically active nucleases |
| US8703489B2 (en) | 2008-08-22 | 2014-04-22 | Sangamo Biosciences, Inc. | Methods and compositions for targeted single-stranded cleavage and targeted integration |
| ES2627552T3 (es) | 2008-12-04 | 2017-07-28 | Sigma Aldrich Company | Edición de genoma en ratas usando nucleasas con dedos de cinc |
| KR101683928B1 (ko) | 2008-12-17 | 2016-12-07 | 다우 아그로사이언시즈 엘엘씨 | Ｚｐ１５ 유전자 자리 내로의 표적화 통합 |
| EP2206723A1 (en) | 2009-01-12 | 2010-07-14 | Bonas, Ulla | Modular DNA-binding domains |
| WO2010090536A2 (en) | 2009-01-15 | 2010-08-12 | The New Zealand Institute For Plant And Food Research Limited | Plant transformation using dna minicircles |
| US8871905B2 (en) | 2009-03-20 | 2014-10-28 | Sangamo Biosciences, Inc. | Modification of CXCR4 using engineered zinc finger proteins |
| CA2756833C (en) * | 2009-04-09 | 2019-11-19 | Sangamo Biosciences, Inc. | Targeted integration into stem cells |
| AU2010275432A1 (en) * | 2009-07-24 | 2012-02-02 | Sigma-Aldrich Co. Llc. | Method for genome editing |
| NZ599998A (en) | 2009-10-16 | 2014-11-28 | Baylor College Medicine | Supercoiled minicircle dna for gene therapy applications |
| EP2534173B1 (en) | 2010-02-08 | 2019-09-11 | Sangamo Therapeutics, Inc. | Engineered cleavage half-domains |
| EP2534163B1 (en) | 2010-02-09 | 2015-11-04 | Sangamo BioSciences, Inc. | Targeted genomic modification with partially single-stranded donor molecules |
| AU2011219716A1 (en) * | 2010-02-26 | 2012-09-27 | Cellectis | Use of endonucleases for inserting transgenes into safe harbor loci |
| CN102939377B (zh) | 2010-04-26 | 2016-06-08 | 桑格摩生物科学股份有限公司 | 使用锌指核酸酶对Rosa位点进行基因组编辑 |
| EP2571512B1 (en) | 2010-05-17 | 2017-08-23 | Sangamo BioSciences, Inc. | Novel dna-binding proteins and uses thereof |
| WO2012015938A2 (en) * | 2010-07-27 | 2012-02-02 | The Johns Hopkins University | Obligate heterodimer variants of foki cleavage domain |
| GB201014169D0 (en) * | 2010-08-25 | 2010-10-06 | Cambridge Entpr Ltd | In vitro hepatic differentiation |
| EP2678434B1 (en) * | 2011-02-25 | 2018-11-07 | Recombinetics, Inc. | Genetically modified animals and methods for making the same |
| KR102061557B1 (ko) * | 2011-09-21 | 2020-01-03 | 상가모 테라퓨틱스, 인코포레이티드 | 이식 유전자 발현의 조절을 위한 방법 및 조성물 |
| AU2012328682B2 (en) | 2011-10-27 | 2017-09-21 | Sangamo Therapeutics, Inc. | Methods and compositions for modification of the HPRT locus |
| MY189533A (en) | 2012-05-25 | 2022-02-16 | Univ California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| BR112014030007A2 (pt) * | 2012-05-30 | 2017-06-27 | Baylor College Medicine | minivetores superenrolados como uma ferramenta para reparação, alteração e substituição de dna |
| AU2013355327A1 (en) * | 2012-12-05 | 2015-06-11 | Sangamo Therapeutics, Inc. | Methods and compositions for regulation of metabolic disorders |
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2014
- 2014-05-06 AU AU2014262867A patent/AU2014262867B2/en not_active Ceased
- 2014-05-06 WO PCT/US2014/036972 patent/WO2014182700A1/en not_active Ceased
- 2014-05-06 US US14/271,008 patent/US10604771B2/en active Active
- 2014-05-06 EP EP14794094.4A patent/EP2994531B1/en active Active
- 2014-05-06 JP JP2016513016A patent/JP2016518142A/ja active Pending
- 2014-05-06 CA CA2910427A patent/CA2910427C/en active Active
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| AU2014262867A1 (en) | 2015-11-12 |
| US10604771B2 (en) | 2020-03-31 |
| JP2016518142A (ja) | 2016-06-23 |
| EP2994531A4 (en) | 2016-11-23 |
| CA2910427A1 (en) | 2014-11-13 |
| EP2994531A1 (en) | 2016-03-16 |
| EP2994531B1 (en) | 2018-03-28 |
| US20140335063A1 (en) | 2014-11-13 |
| AU2014262867B2 (en) | 2019-12-05 |
| WO2014182700A1 (en) | 2014-11-13 |
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