JP2018503387A5 - - Google Patents
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- JP2018503387A5 JP2018503387A5 JP2017540255A JP2017540255A JP2018503387A5 JP 2018503387 A5 JP2018503387 A5 JP 2018503387A5 JP 2017540255 A JP2017540255 A JP 2017540255A JP 2017540255 A JP2017540255 A JP 2017540255A JP 2018503387 A5 JP2018503387 A5 JP 2018503387A5
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Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021082195A JP7114117B2 (ja) | 2015-01-30 | 2021-05-14 | 初代造血細胞におけるタンパク質送達 |
| JP2022115435A JP7356750B2 (ja) | 2015-01-30 | 2022-07-20 | 初代造血細胞におけるタンパク質送達 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562110187P | 2015-01-30 | 2015-01-30 | |
| US62/110,187 | 2015-01-30 | ||
| US201562209711P | 2015-08-25 | 2015-08-25 | |
| US62/209,711 | 2015-08-25 | ||
| PCT/US2016/015836 WO2016123578A1 (en) | 2015-01-30 | 2016-01-29 | Protein delivery in primary hematopoietic cells |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021082195A Division JP7114117B2 (ja) | 2015-01-30 | 2021-05-14 | 初代造血細胞におけるタンパク質送達 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018503387A JP2018503387A (ja) | 2018-02-08 |
| JP2018503387A5 true JP2018503387A5 (https=) | 2019-03-07 |
| JP6886404B2 JP6886404B2 (ja) | 2021-06-16 |
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017540255A Active JP6886404B2 (ja) | 2015-01-30 | 2016-01-29 | 初代造血細胞におけるタンパク質送達 |
| JP2021082195A Active JP7114117B2 (ja) | 2015-01-30 | 2021-05-14 | 初代造血細胞におけるタンパク質送達 |
| JP2022115435A Active JP7356750B2 (ja) | 2015-01-30 | 2022-07-20 | 初代造血細胞におけるタンパク質送達 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021082195A Active JP7114117B2 (ja) | 2015-01-30 | 2021-05-14 | 初代造血細胞におけるタンパク質送達 |
| JP2022115435A Active JP7356750B2 (ja) | 2015-01-30 | 2022-07-20 | 初代造血細胞におけるタンパク質送達 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20190388469A1 (https=) |
| EP (2) | EP3250693B2 (https=) |
| JP (3) | JP6886404B2 (https=) |
| KR (1) | KR102605464B1 (https=) |
| CN (1) | CN107429254B (https=) |
| AU (2) | AU2016211161C1 (https=) |
| ES (1) | ES2880473T5 (https=) |
| IL (1) | IL253498B (https=) |
| SG (1) | SG11201706059SA (https=) |
| WO (1) | WO2016123578A1 (https=) |
Families Citing this family (91)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10323236B2 (en) | 2011-07-22 | 2019-06-18 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| WO2013163628A2 (en) | 2012-04-27 | 2013-10-31 | Duke University | Genetic correction of mutated genes |
| CN112301024A (zh) | 2013-03-15 | 2021-02-02 | 通用医疗公司 | 使用RNA引导的FokI核酸酶(RFN)提高RNA引导的基因组编辑的特异性 |
| US9828582B2 (en) | 2013-03-19 | 2017-11-28 | Duke University | Compositions and methods for the induction and tuning of gene expression |
| US9163284B2 (en) | 2013-08-09 | 2015-10-20 | President And Fellows Of Harvard College | Methods for identifying a target site of a Cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US20150165054A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting caspase-9 point mutations |
| US10077453B2 (en) | 2014-07-30 | 2018-09-18 | President And Fellows Of Harvard College | CAS9 proteins including ligand-dependent inteins |
| US20200332259A1 (en) * | 2014-11-04 | 2020-10-22 | Versiti Blood Research Institute Foundation, Inc. | Method to bioengineer designer red blood cells using gene editing and stem cell methodologies |
| WO2016130600A2 (en) | 2015-02-09 | 2016-08-18 | Duke University | Compositions and methods for epigenome editing |
| CA2986310A1 (en) | 2015-05-11 | 2016-11-17 | Editas Medicine, Inc. | Optimized crispr/cas9 systems and methods for gene editing in stem cells |
| CN108026526B (zh) | 2015-06-09 | 2023-05-12 | 爱迪塔斯医药公司 | 用于改善移植的crispr/cas相关方法和组合物 |
| JP2018518181A (ja) | 2015-06-17 | 2018-07-12 | ザ ユーエービー リサーチ ファンデーション | 血液細胞系列の細胞に機能的ポリペプチドを導入するためのＣＲＩＳＰＲ／Ｃａｓ９複合体 |
| JP2018518182A (ja) | 2015-06-17 | 2018-07-12 | ザ ユーエービー リサーチ ファンデーション | ゲノム編集のためのｃｒｉｓｐｒ／ｃａｓ９複合体 |
| GB2592821B (en) | 2015-07-31 | 2022-01-12 | Univ Minnesota | Modified cells and methods of therapy |
| EP4089175A1 (en) | 2015-10-13 | 2022-11-16 | Duke University | Genome engineering with type i crispr systems in eukaryotic cells |
| IL310721B2 (en) | 2015-10-23 | 2025-11-01 | Harvard College | Nucleobase editors and uses thereof |
| KR102787119B1 (ko) | 2015-11-30 | 2025-03-27 | 듀크 유니버시티 | 유전자 편집에 의한 인간 디스트로핀 유전자의 교정을 위한 치료용 표적 및 사용 방법 |
| JP7033535B2 (ja) * | 2016-01-12 | 2022-03-10 | スクイーズ バイオテクノロジーズ カンパニー | 複合体の細胞内送達 |
| US20190127713A1 (en) | 2016-04-13 | 2019-05-02 | Duke University | Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use |
| JP7490211B2 (ja) | 2016-07-19 | 2024-05-27 | デューク ユニバーシティ | Ｃｐｆ１に基づくゲノム編集の治療適用 |
| CN110214183A (zh) | 2016-08-03 | 2019-09-06 | 哈佛大学的校长及成员们 | 腺苷核碱基编辑器及其用途 |
| WO2018031683A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| BR112019002779A2 (pt) | 2016-08-12 | 2019-05-14 | Toolgen Incorporated | elemento imunorregulador manipulado e imunidade alterada por este |
| US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| KR102622411B1 (ko) | 2016-10-14 | 2024-01-10 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵염기 에디터의 aav 전달 |
| KR20190067209A (ko) * | 2016-10-14 | 2019-06-14 | 더 제너럴 하스피탈 코포레이션 | 후성적으로 조절되는 부위-특이적 뉴클레아제 |
| CA3042179A1 (en) * | 2016-10-31 | 2018-05-03 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Method for treating autoimmune disease using cd4 t-cells with engineered stabilization of expression of endogenous foxp3 gene |
| WO2018111947A1 (en) * | 2016-12-12 | 2018-06-21 | Integrated Dna Technologies, Inc. | Genome editing enhancement |
| WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
| WO2018148603A1 (en) * | 2017-02-09 | 2018-08-16 | Allen Institute | Genetically-tagged stem cell lines and methods of use |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| US12390514B2 (en) | 2017-03-09 | 2025-08-19 | President And Fellows Of Harvard College | Cancer vaccine |
| US11542496B2 (en) | 2017-03-10 | 2023-01-03 | President And Fellows Of Harvard College | Cytosine to guanine base editor |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
| JP7235391B2 (ja) | 2017-05-08 | 2023-03-08 | ツールゲン インコーポレイテッド | 人工的に操作された免疫細胞 |
| 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 |
| WO2018232356A1 (en) * | 2017-06-15 | 2018-12-20 | The Regents Of The University Of California | Targeted non-viral dna insertions |
| US11866726B2 (en) | 2017-07-14 | 2024-01-09 | Editas Medicine, Inc. | Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites |
| 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 |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| WO2019051428A1 (en) * | 2017-09-11 | 2019-03-14 | The Regents Of The University Of California | CAS9 ANTIBODY MEDIA ADMINISTRATION TO MAMMALIAN CELLS |
| KR20250107288A (ko) | 2017-10-16 | 2025-07-11 | 더 브로드 인스티튜트, 인코퍼레이티드 | 아데노신 염기 편집제의 용도 |
| JP7101419B2 (ja) | 2017-10-27 | 2022-07-15 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 内因性ｔ細胞受容体の標的置換 |
| WO2019106522A1 (en) * | 2017-11-28 | 2019-06-06 | Novartis Ag | Pooled crispr/cas9 screening in primary cells using guide swap technology |
| US12406749B2 (en) | 2017-12-15 | 2025-09-02 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| EP3740580A4 (en) | 2018-01-19 | 2021-10-20 | Duke University | GENOME ENGINEERING WITH CRISPR-CAS SYSTEMS IN EUKARYONTS |
| US20190284553A1 (en) | 2018-03-15 | 2019-09-19 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| AU2019261438B2 (en) * | 2018-04-27 | 2024-08-22 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Expression of FOXP3 in edited CD34+ cells |
| CA3091491A1 (en) * | 2018-04-27 | 2019-10-31 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Expression of human foxp3 in gene edited t cells |
| KR20210045360A (ko) | 2018-05-16 | 2021-04-26 | 신테고 코포레이션 | 가이드 rna 설계 및 사용을 위한 방법 및 시스템 |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| WO2020014235A1 (en) | 2018-07-09 | 2020-01-16 | The Regents Of The University Of California | Gene targets for t-cell-based immunotherapy |
| US12522807B2 (en) | 2018-07-09 | 2026-01-13 | The Broad Institute, Inc. | RNA programmable epigenetic RNA modifiers and uses thereof |
| WO2020092453A1 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Nucleobase editors comprising geocas9 and uses thereof |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| CN110527695B (zh) * | 2019-03-07 | 2020-06-16 | 山东舜丰生物科技有限公司 | 一种用于基因定点突变的核酸构建物 |
| WO2020191233A1 (en) | 2019-03-19 | 2020-09-24 | The Broad Institute, Inc. | Methods and compositions for editing nucleotide sequences |
| WO2020198151A1 (en) * | 2019-03-22 | 2020-10-01 | Spotlight Therapeutics | Targeted active gene editing agent and methods of use |
| JP2022524221A (ja) * | 2019-03-22 | 2022-04-28 | スポットライト セラピューティクス | 標的指向活性遺伝子編集剤及び使用方法 |
| WO2020214619A1 (en) * | 2019-04-15 | 2020-10-22 | Emendobio Inc. | Crispr compositions and methods for promoting gene editing of gata2 |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| WO2021062201A1 (en) * | 2019-09-25 | 2021-04-01 | Spotlight Therapeutics | Compositions and methods for nucleoprotein targeting and expression |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| IL297761A (en) | 2020-05-08 | 2022-12-01 | Broad Inst Inc | Methods and compositions for simultaneously editing two helices of a designated double-helix nucleotide sequence |
| WO2022125633A1 (en) * | 2020-12-08 | 2022-06-16 | The Regents Of The University Of California | Crispr ribonucleoprotein complex genome editing of human innate immune cells |
| US20240252684A1 (en) | 2021-07-30 | 2024-08-01 | Tune Therapeutics, Inc. | Compositions and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) |
| CA3227103A1 (en) | 2021-07-30 | 2023-02-02 | Matthew P. GEMBERLING | Compositions and methods for modulating expression of frataxin (fxn) |
| JP2024537991A (ja) | 2021-10-14 | 2024-10-18 | アーセナル バイオサイエンシズ インコーポレイテッド | 共発現されるｓｈＲＮＡと論理ゲートシステムとを有する免疫細胞 |
| KR20230107750A (ko) * | 2022-01-07 | 2023-07-18 | 주식회사 툴젠 | 유전자 편집 과정에서 발생 가능한 오프 타겟을 예측하는 방법 |
| US20250154503A1 (en) | 2022-01-14 | 2025-05-15 | Tune Therapeutics, Inc. | Compositions, systems, and methods for programming t cell phenotypes through targeted gene repression |
| US20250134999A1 (en) | 2022-01-14 | 2025-05-01 | Tune Therapeutics, Inc. | Compositions, systems, and methods for programming t cell phenotypes through targeted gene activation |
| IL317874A (en) | 2022-06-24 | 2025-02-01 | Tune Therapeutics Inc | Compounds, systems and methods for reducing low density lipoproteins through targeted gene suppression |
| CA3261865A1 (en) | 2022-07-12 | 2024-01-18 | Tune Therapeutics, Inc. | TARGETED TRANSCRIPTIONAL ACTIVATION COMPOSITIONS, SYSTEMS AND METHODS |
| KR20250077608A (ko) | 2022-08-19 | 2025-05-30 | 튠 쎄라퓨틱스, 인코포레이티드 | 표적 유전자 억제를 통한 b형 간염 바이러스 조절용 조성물, 시스템 및 방법 |
| WO2024064642A2 (en) | 2022-09-19 | 2024-03-28 | Tune Therapeutics, Inc. | Compositions, systems, and methods for modulating t cell function |
| EP4634383A1 (en) * | 2022-12-16 | 2025-10-22 | Life Edit Therapeutics, Inc. | Guide rnas that target foxp3 gene and methods of use |
| WO2024163683A2 (en) | 2023-02-01 | 2024-08-08 | Tune Therapeutics, Inc. | Systems, compositions, and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) and x-inactive specific transcript (xist) |
| WO2024163678A2 (en) | 2023-02-01 | 2024-08-08 | Tune Therapeutics, Inc. | Fusion proteins and systems for targeted activation of frataxin (fxn) and related methods |
| CN116496992B (zh) * | 2023-04-24 | 2023-12-01 | 江苏省家禽科学研究所 | 一种鸡胚成肌永生化细胞及其构建方法和应用 |
| CN121909284A (zh) | 2023-07-31 | 2026-04-21 | 图恩疗法股份有限公司 | 用于调节il-2基因表达的组合物和方法 |
| WO2025029840A1 (en) | 2023-07-31 | 2025-02-06 | Tune Therapeutics, Inc. | Compositions and methods for multiplexed activation and repression of t cell gene expression |
| WO2025038494A1 (en) | 2023-08-11 | 2025-02-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for lymphoid cell differentiation using targeted gene activation |
| WO2025059073A1 (en) | 2023-09-11 | 2025-03-20 | Tune Therapeutics, Inc. | Epigenetic editing methods and systems for differentiating stem cells |
| CN117448330B (zh) * | 2023-10-25 | 2025-01-21 | 山东省农业科学院家禽研究所（山东省无特定病原鸡研究中心） | Acsl4基因缺失的mdck纯合子细胞系的构建方法和应用 |
| WO2025260068A1 (en) | 2024-06-14 | 2025-12-18 | Tune Therapeutics, Inc. | Lipid nanoparticle formulation for delivery of nucleic acids to cells |
| WO2026015647A1 (en) | 2024-07-09 | 2026-01-15 | Tune Therapeutics, Inc. | Compositions, systems, and methods for cell differentiation using targeted gene activation of dll4 and/or vcam1 |
| WO2026064753A1 (en) | 2024-09-23 | 2026-03-26 | Tune Therapeutics, Inc. | Dna methyltransferase-like protein (dnmt3l) or dna methyltransferase 3a (dnmt3a) repressor systems for epigenetic editing |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US702996A (en) | 1901-12-05 | 1902-06-24 | Wladyslaw Pruszkowski | Alloy. |
| US6773669B1 (en) | 1995-03-10 | 2004-08-10 | Maxcyte, Inc. | Flow electroporation chamber and method |
| US6090617A (en) | 1996-12-05 | 2000-07-18 | Entremed, Inc. | Flow electroporation chamber with electrodes having a crystalline metal nitride coating |
| US6410319B1 (en) | 1998-10-20 | 2002-06-25 | City Of Hope | CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies |
| US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
| WO2002085923A2 (en) | 2001-04-19 | 2002-10-31 | The Scripps Research Institute | In vivo incorporation of unnatural amino acids |
| CN1302115C (zh) | 2001-04-23 | 2007-02-28 | 埃麦克萨有限公司 | 电穿孔用缓冲溶液及上述溶液的使用方法 |
| AU2002326717A1 (en) | 2001-08-22 | 2003-03-10 | Maxcyte, Inc. | Apparatus and method for electroporation of biological samples |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
| DE502004009820D1 (de) | 2004-03-15 | 2009-09-10 | Lonza Cologne Ag | Behältnis und Vorrichtung zur Erzeugung von elektrischen Feldern in einzelnen Reaktionsräumen |
| US7771984B2 (en) | 2004-05-12 | 2010-08-10 | Maxcyte, Inc. | Methods and devices related to a regulated flow electroporation chamber |
| JP4519915B2 (ja) | 2004-06-12 | 2010-08-04 | インビトロゲン シンガポール ピーティーイー．リミテッド． | 中空構造を有する電気穿孔装置 |
| ES2465467T3 (es) | 2004-06-14 | 2014-06-05 | Lonza Cologne Ag | Procedimiento y disposición de circuito para el tratamiento de material biológico |
| US7991559B2 (en) | 2004-11-30 | 2011-08-02 | Maxcyte Inc. | Computerized electroporation |
| US8044019B2 (en) | 2005-10-28 | 2011-10-25 | Mitsubishi Tanabe Pharma Corporation | Cell penetrating peptide |
| US8450112B2 (en) | 2008-04-09 | 2013-05-28 | Maxcyte, Inc. | Engineering and delivery of therapeutic compositions of freshly isolated cells |
| WO2009147368A1 (en) | 2008-06-04 | 2009-12-10 | Medical Research Council | Peptides |
| US20120088842A1 (en) | 2008-07-18 | 2012-04-12 | Maxcyte, Inc. | Methods for optimizing electroporation |
| EP2331566B1 (en) | 2008-08-26 | 2015-10-07 | City of Hope | Method and compositions for enhanced anti-tumor effector functioning of t cells |
| US8389481B2 (en) | 2008-11-12 | 2013-03-05 | University Of Medicine And Dentistry Of New Jersey | Glutamate-enhanced cell-penetrating peptides and methods of using same |
| WO2010121130A2 (en) | 2009-04-16 | 2010-10-21 | President And Fellows Of Harvard College | Molecular delivery with nanowires |
| RU2548807C2 (ru) | 2009-05-20 | 2015-04-20 | Торэй Индастриз, Инк. | Пептиды, проникающие в клетку |
| US8372951B2 (en) | 2010-05-14 | 2013-02-12 | National Tsing Hua University | Cell penetrating peptides for intracellular delivery |
| US9987308B2 (en) | 2011-03-23 | 2018-06-05 | Fred Hutchinson Cancer Research Center | Method and compositions for cellular immunotherapy |
| WO2013051718A1 (ja) | 2011-10-07 | 2013-04-11 | 国立大学法人三重大学 | キメラ抗原受容体 |
| PT2768942T (pt) | 2011-10-17 | 2020-01-21 | Massachusetts Inst Technology | Entrega intracelular |
| ES2654060T3 (es) | 2011-10-20 | 2018-02-12 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Receptores de antígenos quiméricos anti-CD22 |
| EP2828290B1 (en) | 2012-03-23 | 2018-08-15 | The United States of America, represented by the Secretary, Department of Health and Human Services | Anti-mesothelin chimeric antigen receptors |
| AU2013266968B2 (en) * | 2012-05-25 | 2017-06-29 | Emmanuelle CHARPENTIER | Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription |
| US8614194B1 (en) | 2012-07-25 | 2013-12-24 | Kaohsiung Medical University | Anionic cell penetrating peptide and its use for intracellular delivery |
| WO2014031173A1 (en) | 2012-08-22 | 2014-02-27 | President And Fellows Of Harvard College | Multiwell plates comprising nanowires |
| EP2931899A1 (en) * | 2012-12-12 | 2015-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| CN113684185A (zh) | 2013-02-26 | 2021-11-23 | 纪念斯隆-凯特琳癌症中心 | 用于免疫疗法的组合物和方法 |
| WO2014191128A1 (en) * | 2013-05-29 | 2014-12-04 | Cellectis | Methods for engineering t cells for immunotherapy by using rna-guided cas nuclease system |
| JP6598860B2 (ja) | 2014-08-06 | 2019-10-30 | カレッジ オブ メディシン ポチョン チャ ユニバーシティ インダストリー−アカデミック コーオペレイション ファウンデーション | Ｈｌａをコードする遺伝子のヌクレアーゼ媒介編集により作製される免疫適合性細胞 |
-
2016
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