TWI716367B - 用於常間回文重複序列叢集(crispr)之大量平行組合性基因學 - Google Patents
用於常間回文重複序列叢集(crispr)之大量平行組合性基因學 Download PDFInfo
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| ES2884838T3 (es) | 2015-04-06 | 2021-12-13 | Univ Leland Stanford Junior | ARN guía químicamente modificados para la regulación génica mediada por CRISPR/CAS |
| US12043852B2 (en) | 2015-10-23 | 2024-07-23 | President And Fellows Of Harvard College | Evolved Cas9 proteins for gene editing |
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| US10752904B2 (en) * | 2016-04-26 | 2020-08-25 | Massachusetts Institute Of Technology | Extensible recombinase cascades |
| US10767175B2 (en) | 2016-06-08 | 2020-09-08 | Agilent Technologies, Inc. | High specificity genome editing using chemically modified guide RNAs |
| DK3474669T3 (da) | 2016-06-24 | 2022-06-27 | Univ Colorado Regents | Fremgangsmåde til generering af stregkodede kombinatoriske biblioteker |
| WO2018005691A1 (en) * | 2016-06-29 | 2018-01-04 | The Regents Of The University Of California | Efficient genetic screening method |
| KR20250103795A (ko) | 2016-08-03 | 2025-07-07 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 아데노신 핵염기 편집제 및 그의 용도 |
| CN109804066A (zh) | 2016-08-09 | 2019-05-24 | 哈佛大学的校长及成员们 | 可编程cas9-重组酶融合蛋白及其用途 |
| WO2018035495A1 (en) | 2016-08-19 | 2018-02-22 | Whitehead Institute For Biomedical Research | Methods of editing dna methylation |
| US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| WO2018049075A1 (en) | 2016-09-07 | 2018-03-15 | Flagship Pioneering, Inc. | Methods and compositions for modulating gene expression |
| AU2017342543B2 (en) | 2016-10-14 | 2024-06-27 | President And Fellows Of Harvard College | AAV delivery of nucleobase editors |
| US20200149039A1 (en) | 2016-12-12 | 2020-05-14 | Whitehead Institute For Biomedical Research | Regulation of transcription through ctcf loop anchors |
| WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
| JP7142637B2 (ja) * | 2016-12-29 | 2022-09-27 | ヨハン ウォルフガング ゲーテ-ウニベルジテート フランクフルト アム マイン | より高次のゲノム編集ライブラリーを生成する方法 |
| FI3565891T3 (fi) | 2017-01-09 | 2023-07-04 | Whitehead Inst Biomedical Res | Menetelmiä geeniekspression muuttamiseksi häiritsemällä säätelysilmukoita muodostavia transkriptiotekijämultimeerejä |
| US10995333B2 (en) | 2017-02-06 | 2021-05-04 | 10X Genomics, Inc. | Systems and methods for nucleic acid preparation |
| WO2018145041A1 (en) * | 2017-02-06 | 2018-08-09 | 10X Genomics, Inc. | Systems and methods for nucleic acid preparation |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| EP3592381A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Cancer vaccine |
| KR20190127797A (ko) | 2017-03-10 | 2019-11-13 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 시토신에서 구아닌으로의 염기 편집제 |
| CA3057192A1 (en) | 2017-03-23 | 2018-09-27 | President And Fellows Of Harvard College | Nucleobase editors comprising nucleic acid programmable dna binding proteins |
| WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
| US10011849B1 (en) | 2017-06-23 | 2018-07-03 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| US9982279B1 (en) | 2017-06-23 | 2018-05-29 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| CN111801345A (zh) | 2017-07-28 | 2020-10-20 | 哈佛大学的校长及成员们 | 使用噬菌体辅助连续进化(pace)的进化碱基编辑器的方法和组合物 |
| KR20200033259A (ko) | 2017-07-31 | 2020-03-27 | 리제너론 파마슈티칼스 인코포레이티드 | 생체내에서 CRISPR/Cas-매개된 파괴 또는 삭제 및 외인성 도너 핵산과의 CRISPR/Cas-유도된 재조합을 평가하기 위한 방법 및 조성물 |
| KR102780441B1 (ko) | 2017-07-31 | 2025-03-17 | 리제너론 파마슈티칼스 인코포레이티드 | Cas-형질전환 마우스 배아 줄기 세포 및 마우스 및 이것의 용도 |
| WO2019139645A2 (en) | 2017-08-30 | 2019-07-18 | President And Fellows Of Harvard College | High efficiency base editors comprising gam |
| CA3082251A1 (en) | 2017-10-16 | 2019-04-25 | The Broad Institute, Inc. | Uses of adenosine base editors |
| WO2019089803A1 (en) * | 2017-10-31 | 2019-05-09 | The Broad Institute, Inc. | Methods and compositions for studying cell evolution |
| EP3724214A4 (en) | 2017-12-15 | 2021-09-01 | The Broad Institute Inc. | SYSTEMS AND METHODS FOR PREDICTING REPAIR RESULTS IN GENETIC ENGINEERING |
| WO2019226953A1 (en) | 2018-05-23 | 2019-11-28 | The Broad Institute, Inc. | Base editors and uses thereof |
| US20210308171A1 (en) * | 2018-08-07 | 2021-10-07 | The Broad Institute, Inc. | Methods for combinatorial screening and use of therapeutic targets thereof |
| EP3853363A4 (en) | 2018-09-19 | 2022-12-14 | The University of Hong Kong | ENHANCED HIGH THROUGHPUT COMBINATORY GENE MODIFICATION SYSTEM AND OPTIMIZED CAS9 ENZYME VARIANTS |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| JP7144618B2 (ja) * | 2018-12-20 | 2022-09-29 | 北京大学 | バーコード付きガイドrna構築体を使用する効率的な遺伝子スクリーニングのための組成物及び方法 |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| DE112020001306T5 (de) | 2019-03-19 | 2022-01-27 | Massachusetts Institute Of Technology | Verfahren und zusammensetzungen zur editierung von nukleotidsequenzen |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| US11987791B2 (en) | 2019-09-23 | 2024-05-21 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (HNF4α) gene expression |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| CN110652589A (zh) * | 2019-10-12 | 2020-01-07 | 中国人民解放军陆军军医大学 | Gasc1抑制剂在制备治疗肝癌的药物中的应用 |
| US20230002756A1 (en) * | 2019-12-12 | 2023-01-05 | The Trustees Of The University Of Pennsylvania | High Performance Platform for Combinatorial Genetic Screening |
| US20230227814A1 (en) | 2020-04-16 | 2023-07-20 | The University Of Hong Kong | System for three-way combinatorial crispr screens for analysing target interactions and methods thereof |
| JP2023525304A (ja) | 2020-05-08 | 2023-06-15 | ザ ブロード インスティテュート,インコーポレーテッド | 標的二本鎖ヌクレオチド配列の両鎖同時編集のための方法および組成物 |
| WO2022159402A1 (en) * | 2021-01-19 | 2022-07-28 | The Board Of Trustees Of The Leland Stanford Junior University | Composition and method for high-multiplexed genome engineering using synthetic crispr arrays |
| WO2022195582A1 (en) * | 2021-03-15 | 2022-09-22 | G.T.A.I Innovation Ltd. | A method and apparatus for lab tests |
| CN113599522B (zh) * | 2021-08-03 | 2022-09-20 | 深圳市北科生物科技有限公司 | Kdm6作为靶标在制备用于提高早期神经外胚层分化效率的药物中的应用 |
| US11884915B2 (en) | 2021-09-10 | 2024-01-30 | Agilent Technologies, Inc. | Guide RNAs with chemical modification for prime editing |
| CN116019811B (zh) * | 2023-02-07 | 2024-04-12 | 华中科技大学协和深圳医院 | Gsk-j4用于制备抗革兰氏阳性菌感染药物中的应用 |
| CN118425525B (zh) * | 2024-03-13 | 2025-08-22 | 郑州大学第一附属医院 | Kdm5b在肾纤维化治疗中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013176772A1 (en) * | 2012-05-25 | 2013-11-28 | The Regents Of The University Of California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| WO2014005042A2 (en) * | 2012-06-29 | 2014-01-03 | Massachusetts Institute Of Technology | Massively parallel combinatorial genetics |
| WO2014093694A1 (en) * | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1629096A1 (en) * | 2004-05-10 | 2006-03-01 | BASF Plant Science GmbH | Methods for assembling multiple expression constructs |
| CN101910182B (zh) * | 2007-12-28 | 2013-07-17 | 田边三菱制药株式会社 | 抗癌剂 |
| CA2799403C (en) * | 2010-05-14 | 2020-01-21 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating leukemia |
| AR084070A1 (es) * | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| CN103516916B (zh) | 2012-06-28 | 2018-03-27 | 中兴通讯股份有限公司 | 拨号方法及装置 |
| MX2015003959A (es) * | 2012-10-02 | 2015-11-16 | Epitherapeutics Aps | Inhibidores de histona demetilasas. |
| WO2014080290A2 (en) * | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Cyclic amines as bromodomain inhibitors |
| CN103833671B (zh) * | 2012-11-27 | 2016-12-21 | 中国科学院上海药物研究所 | 一类二氢噻唑酮类化合物及其药物组合物和用途 |
| PT3363902T (pt) * | 2012-12-06 | 2019-12-19 | Sigma Aldrich Co Llc | Modificação e regulação de genoma baseadas em crispr |
| US8697359B1 (en) * | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| KR20150105956A (ko) * | 2012-12-12 | 2015-09-18 | 더 브로드 인스티튜트, 인코퍼레이티드 | 서열 조작 및 치료적 적용을 위한 시스템, 방법 및 조성물의 전달, 유전자 조작 및 최적화 |
| AU2014235794A1 (en) * | 2013-03-14 | 2015-10-22 | Caribou Biosciences, Inc. | Compositions and methods of nucleic acid-targeting nucleic acids |
| JP6370368B2 (ja) | 2013-03-27 | 2018-08-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Brd4阻害剤としてのインドリノン類似体 |
| JP6738729B2 (ja) * | 2013-06-17 | 2020-08-12 | ザ・ブロード・インスティテュート・インコーポレイテッド | 分裂終了細胞の疾患および障害をターゲティングおよびモデリングするための系、方法および組成物の送達、エンジニアリングおよび最適化 |
| EP3540051B1 (en) * | 2013-12-12 | 2022-08-17 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hsv and viral diseases and disorders. |
| BR112016013201B1 (pt) * | 2013-12-12 | 2023-01-31 | The Broad Institute, Inc. | Uso de uma composição compreendendo um sistema crispr-cas no tratamento de uma doença genética ocular |
| EP3079726B1 (en) * | 2013-12-12 | 2018-12-05 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using particle delivery components |
| WO2015095501A1 (en) * | 2013-12-18 | 2015-06-25 | Onn Brandman | Pooled method for high throughput screening of trans factors affecting rna levels |
| WO2015153940A1 (en) * | 2014-04-03 | 2015-10-08 | Massachusetts Institute Of Technology | Methods and compositions for the production of guide rna |
| US20170044107A1 (en) * | 2014-04-28 | 2017-02-16 | The J. David Gladstone Institutes | Inhibitors of JMJD2C as Anticancer Agents |
| US20170232030A1 (en) * | 2014-08-13 | 2017-08-17 | Epizyme, Inc. | Combination therapy for treating cancer |
| WO2016049024A2 (en) * | 2014-09-24 | 2016-03-31 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling competition of multiple cancer mutations in vivo |
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- 2015-10-30 TW TW104135960A patent/TWI716367B/zh active
- 2015-10-30 DK DK15813148.2T patent/DK3212789T3/da active
- 2015-10-30 EP EP20167714.3A patent/EP3708155A1/en not_active Withdrawn
-
2021
- 2021-06-03 US US17/338,027 patent/US20210310022A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013176772A1 (en) * | 2012-05-25 | 2013-11-28 | The Regents Of The University Of California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| WO2014005042A2 (en) * | 2012-06-29 | 2014-01-03 | Massachusetts Institute Of Technology | Massively parallel combinatorial genetics |
| WO2014093694A1 (en) * | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107429246A (zh) | 2017-12-01 |
| EP3212789B1 (en) | 2020-04-22 |
| WO2016070037A3 (en) | 2016-06-23 |
| CN107429246B (zh) | 2021-06-01 |
| EP3708155A1 (en) | 2020-09-16 |
| JP2017534285A (ja) | 2017-11-24 |
| JP6788584B2 (ja) | 2020-11-25 |
| EP3212789A2 (en) | 2017-09-06 |
| US20210310022A1 (en) | 2021-10-07 |
| WO2016070037A8 (en) | 2017-03-02 |
| US20190100769A1 (en) | 2019-04-04 |
| DK3212789T3 (da) | 2020-07-27 |
| WO2016070037A2 (en) | 2016-05-06 |
| HK1243456A1 (en) | 2018-07-13 |
| TW201631155A (zh) | 2016-09-01 |
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