JP2022001051A - HIV−1プロウイルスDNAのin vivo切除のための組成物及び方法 - Google Patents
HIV−1プロウイルスDNAのin vivo切除のための組成物及び方法 Download PDFInfo
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Abstract
【解決手段】真核細胞における標的のヒト免疫不全ウイルス1(HIV-1)のDNA配列の機能又は存在を阻害する方法であって、標的HIV-1 DNA配列を保有する真核細胞を、(a) 一種以上のガイドRNA、又は前記一種以上のガイドRNAをコードする核酸、及び(b) casタンパク質、又は前記casタンパク質をコードする核酸と接触させる工程を含み、前記ガイドRNAが前記標的HIV-1 DNA配列とハイブリダイズし、これにより前記標的HIV-1 DNA配列の機能又は存在を阻害するものである、方法。
【選択図】図4A
Description
EVDGVDEVAKKKSKK (配列番号26) (Schreiberら(1992) EMBO J. 11:3263-3269)又はステロイドホルモン受容体(ヒト)グルココルチコイドの配列RKCLQAGMNLEARKTKK (配列番号27) (Cadepondら(1992) Exp. Cell Res. 201:99-108)等の二分核局在配列を用いることも可能である。ある実施態様において、NLSはcasタンパク質のN末端に局在する。他の実施態様において、NLSはcasタンパク質のC末端に局在する。
HIV-1プロウイルスの長鎖末端反復領域内に位置する5種類の特定の領域の一つに特異的に結合するガイドRNA分子をコードするプラスミドDNAを作製する(図1)。同様に、cas9ヌクレアーゼをコードするプラスミドを作製する。両方のプラスミドをヒト細胞に送達し、そこでcas9及びガイドRNA遺伝子座が転写され、cas9転写産物は翻訳される。続いて、ガイドRNA部分がcas9ヌクレアーゼに結合し、ハイブリッド複合体を形成する。核局在配列を加えているので、このハイブリッド複合体は核内に入り、核においてガイドRNA部分がHIV-1プロウイルスDNA内の相補配列に結合する。ヌクレアーゼがプロウイルスDNAを切り、通常修復不可能な二重らせんDNA切片をもたらす。図2を参照。この方法を用いることにより、HIV-1プロウイルスDNAを感染細胞のゲノムから切除することができる。
J-Lat細胞株(ヒトT細胞がん株)を用いて、ガイドRNA:hCas9複合体によるHIV-1長鎖末端反復(LTR)の切断がこれらの細胞の転写活性を変化させるか否かを決定した。フローサイトメトリーを用いてトランスフェクション22時間後にLTRプロモーター由来の緑色蛍光タンパク質(GFP)を生産する細胞を定量した。フローサイトメトリー解析により、GFPを発現する細胞の割合が得られ、またGFP+細胞の平均蛍光強度(MFI)を定量することにより細胞群内の発現の強度を定量することもできる。フローサイトメトリーにより、転写を減少させるLTR領域内の変異と、転写を完全に消失させるLTR領域内の変異とを識別することができる。
CRISPR/Cas法のHIV-1 LTR内での切断及び転写の改変の有効性を決定するために、Jurkat細胞を3種類の異なるプラスミドでトランスフェクションした。これらのプラスミドには、様々なガイドRNA、ヒト化Cas9プラスミド、及び無傷のHIV-1 LTR及び5'配列がGFPの発現を促進する第3の(レポーター)プラスミドが含まれる。
Claims (13)
- (a) 標的のヒト免疫不全ウイルス1(HIV-1)のDNA配列とハイブリダイズする一種以上のガイドRNA、又は前記一種以上のガイドRNAをコードする核酸;及び
(b) 規則的な間隔をもってクラスター化された短鎖反復回文配列関連(Clustered Regularly Interspaced Short Palindromic Repeats-Associated:cas)タンパク質;又は前記タンパク質をコードする核酸
を含むキットであって、標的HIV-1 DNA配列が、配列番号3、配列番号4、及び配列番号6で示される塩基配列から成る群から選択され、
前記casタンパク質がCas9である、キット。 - 前記一種以上のガイドRNAをコードする核酸であって、発現ベクター及びウイルスベクターから成る群から選択されるベクターに包含される核酸を含み、
前記casタンパク質をコードする核酸であって、発現ベクター及びウイルスベクターから成る群から選択されるベクターに包含される核酸を含む、請求項1に記載のキット。 - 前記標的HIV-1 DNA配列が配列番号4で示される塩基配列であり、前記一種以上のガイドRNA、又は前記一種以上のガイドRNAをコードする核酸が配列番号4で示される塩基配列又はその相補配列を含む、請求項2に記載のキット。
- 前記一種以上のガイドRNAをコードする核酸、及び前記casタンパク質をコードする核酸を含み、前記一種以上のガイドRNAをコードする核酸、及び前記casタンパク質をコードする核酸のそれぞれが、発現ベクター及びウイルスベクターから成る群から選択される同じベクターに包含される、請求項1に記載のキット。
- 前記casタンパク質がヒト細胞での発現用にコドン最適化されている、請求項1に記載のキット。
- 前記casタンパク質が核局在配列をさらに含む、請求項1に記載のキット。
- 一種以上のガイドRNAをコードする核酸を含み、前記ガイドRNAが配列番号3、配列番号4、及び配列番号6で示される塩基配列から成る群から選択される標的のヒト免疫不全ウイルス1のDNA配列とハイブリダイズする、ベクター。
- 発現ベクターである、請求項7に記載のベクター。
- ウイルスベクターである、請求項7に記載のベクター。
- casタンパク質をコードする核酸をさらに含む、請求項7に記載のベクター。
- 前記casタンパク質がCas9である、請求項10に記載のベクター。
- 前記casタンパク質がヒト細胞での発現用にコドン最適化されている、請求項10に記載のベクター。
- 前記casタンパク質が核局在配列をさらに含む、請求項10に記載のベクター。
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Families Citing this family (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3613852A3 (en) | 2011-07-22 | 2020-04-22 | President and Fellows of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
ES2883590T3 (es) | 2012-12-12 | 2021-12-09 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas |
ES2701749T3 (es) | 2012-12-12 | 2019-02-25 | Broad Inst Inc | Métodos, modelos, sistemas y aparatos para identificar secuencias diana para enzimas Cas o sistemas CRISPR-Cas para secuencias diana y transmitir resultados de los mismos |
AU2014207618A1 (en) | 2013-01-16 | 2015-08-06 | Emory University | Cas9-nucleic acid complexes and uses related thereto |
JP6576904B2 (ja) * | 2013-04-04 | 2019-09-18 | トラスティーズ・オブ・ダートマス・カレッジ | HIV−1プロウイルスDNAのinvivo切除のための組成物及び方法 |
CN105793425B (zh) | 2013-06-17 | 2021-10-26 | 布罗德研究所有限公司 | 使用病毒组分靶向障碍和疾病的crispr-cas系统和组合物的递送、用途和治疗应用 |
CN105492611A (zh) | 2013-06-17 | 2016-04-13 | 布罗德研究所有限公司 | 用于序列操纵的优化的crispr-cas双切口酶系统、方法以及组合物 |
EP3725885A1 (en) | 2013-06-17 | 2020-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
RU2716420C2 (ru) | 2013-06-17 | 2020-03-11 | Те Брод Инститьют Инк. | Доставка и применение систем crispr-cas, векторов и композиций для целенаправленного воздействия и терапии в печени |
CA2915834A1 (en) | 2013-06-17 | 2014-12-24 | Massachusetts Institute Of Technology | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | 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 |
EA037850B1 (ru) | 2013-08-29 | 2021-05-27 | Тэмпл Юниверсити Оф Зе Коммонвэлс Систем Оф Хайе Эдьюкейшн | Способы и композиции для рнк-направленного лечения вич-инфекции |
US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
US9340799B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | MRNA-sensing switchable gRNAs |
US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
DK3066201T3 (en) | 2013-11-07 | 2018-06-06 | Editas Medicine Inc | CRISPR-RELATED PROCEDURES AND COMPOSITIONS WITH LEADING GRADES |
WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
US20150166982A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting pi3k point mutations |
BR112016013207A2 (pt) * | 2013-12-12 | 2017-09-26 | Massachusetts Inst Technology | administração, uso e aplicações terapêuticas dos sistemas crispr-cas e composições para o hbv e distúrbios e doenças virais |
WO2015089486A2 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
AU2014361781B2 (en) | 2013-12-12 | 2021-04-01 | Massachusetts Institute Of Technology | Delivery, use and therapeutic applications of the CRISPR -Cas systems and compositions for genome editing |
JP6712948B2 (ja) | 2013-12-12 | 2020-06-24 | ザ・ブロード・インスティテュート・インコーポレイテッド | 組成物、及びヌクレオチドリピート障害におけるcrispr−cas系の使用方法 |
US10066241B2 (en) | 2014-05-30 | 2018-09-04 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods of delivering treatments for latent viral infections |
WO2016022363A2 (en) | 2014-07-30 | 2016-02-11 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
CN107530399B (zh) * | 2014-10-10 | 2022-03-18 | 马萨诸塞眼科耳科诊所 | 治疗分子在体外和体内的有效递送 |
US20180334732A1 (en) * | 2014-11-25 | 2018-11-22 | Drexel University | Compositions and methods for hiv quasi-species excision from hiv-1-infected patients |
CN107250148B (zh) | 2014-12-03 | 2021-04-16 | 安捷伦科技有限公司 | 具有化学修饰的指导rna |
EP3985115A1 (en) | 2014-12-12 | 2022-04-20 | The Broad Institute, Inc. | Protected guide rnas (pgrnas) |
MA41382A (fr) * | 2015-03-20 | 2017-11-28 | Univ Temple | Édition génique basée sur le système crispr/endonucléase à induction par tat |
KR102648489B1 (ko) | 2015-04-06 | 2024-03-15 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | Crispr/cas-매개 유전자 조절을 위한 화학적으로 변형된 가이드 rna |
US10563226B2 (en) | 2015-05-13 | 2020-02-18 | Seattle Children's Hospital | Enhancing endonuclease based gene editing in primary cells |
US20160348074A1 (en) * | 2015-05-29 | 2016-12-01 | Agenovir Corporation | Methods and compositions for treating cells for transplant |
US10117911B2 (en) | 2015-05-29 | 2018-11-06 | Agenovir Corporation | Compositions and methods to treat herpes simplex virus infections |
EP3324999A1 (en) * | 2015-05-29 | 2018-05-30 | Agenovir Corporation | Compositions and methods for cell targeted hpv treatment |
DK3302709T3 (da) | 2015-06-01 | 2021-08-23 | Univ Temple | Fremgangsmåder og sammensætninger til rna-guidet behandling af hiv-infektion |
CN108290933A (zh) | 2015-06-18 | 2018-07-17 | 布罗德研究所有限公司 | 降低脱靶效应的crispr酶突变 |
WO2016205759A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation |
EP3356521A4 (en) * | 2015-09-28 | 2019-03-13 | Temple University - Of The Commonwealth System of Higher Education | METHOD AND COMPOSITIONS FOR RNA-TREATED TREATMENT OF HIV INFECTIONS |
CA3001130A1 (en) * | 2015-10-16 | 2017-04-20 | Temple University - Of The Commonwealth System Of Higher Education | Methods and compositions utilizing cpf1 for rna-guided gene editing |
JP7109784B2 (ja) | 2015-10-23 | 2022-08-01 | 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 | 遺伝子編集のための進化したCas9蛋白質 |
CA3011874A1 (en) * | 2016-01-25 | 2017-08-03 | Excision Biotherapeutics, Inc. | Methods and compositions for rna-guided treatment of hiv infection |
EP3219799A1 (en) | 2016-03-17 | 2017-09-20 | IMBA-Institut für Molekulare Biotechnologie GmbH | Conditional crispr sgrna expression |
JP2019519250A (ja) * | 2016-05-10 | 2019-07-11 | ユナイテッド ステイツ ガバメント アズ リプレゼンテッド バイ ザ デパートメント オブ ベテランズ アフェアーズUnited States Government As Represented By The Department Of Veterans Affairs | Hiv−1感染と複製に必須な遺伝子を切断するcrispr/casの構築物のレンチウィルスによる送達 |
US10767175B2 (en) | 2016-06-08 | 2020-09-08 | Agilent Technologies, Inc. | High specificity genome editing using chemically modified guide RNAs |
WO2018027078A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harard College | Adenosine nucleobase editors and uses thereof |
US11661590B2 (en) | 2016-08-09 | 2023-05-30 | President And Fellows Of Harvard College | Programmable CAS9-recombinase fusion proteins and uses thereof |
US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
WO2018071868A1 (en) | 2016-10-14 | 2018-04-19 | President And Fellows Of Harvard College | Aav delivery of nucleobase editors |
WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
TW201839136A (zh) | 2017-02-06 | 2018-11-01 | 瑞士商諾華公司 | 治療血色素異常症之組合物及方法 |
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 |
CA3057192A1 (en) | 2017-03-23 | 2018-09-27 | President And Fellows Of Harvard College | Nucleobase editors comprising nucleic acid programmable dna binding proteins |
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 |
US11732274B2 (en) | 2017-07-28 | 2023-08-22 | President And Fellows Of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (PACE) |
US11319532B2 (en) | 2017-08-30 | 2022-05-03 | 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 |
MX2021011426A (es) | 2019-03-19 | 2022-03-11 | Broad Inst Inc | Metodos y composiciones para editar secuencias de nucleótidos. |
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 |
CA3185970A1 (en) * | 2020-07-13 | 2022-01-20 | Alexandra L. Howell | Methods and compositions for crispr/cas9 guide rna efficiency and specificity against genetically diverse hiv-1 isolates |
AU2022343300A1 (en) | 2021-09-10 | 2024-04-18 | Agilent Technologies, Inc. | Guide rnas with chemical modification for prime editing |
JP7388586B1 (ja) | 2023-03-20 | 2023-11-29 | 三菱電機ビルソリューションズ株式会社 | エレベーターシステム |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6576904B2 (ja) * | 2013-04-04 | 2019-09-18 | トラスティーズ・オブ・ダートマス・カレッジ | HIV−1プロウイルスDNAのinvivo切除のための組成物及び方法 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
US5866701A (en) | 1988-09-20 | 1999-02-02 | The Board Of Regents For Northern Illinois University Of Dekalb | HIV targeted hairpin ribozymes |
DK0452457T3 (da) | 1989-11-03 | 1998-03-02 | Univ Vanderbilt | Fremgangsmåde til in vivo fjernelse af funktionelle fremmede gener |
US5670488A (en) | 1992-12-03 | 1997-09-23 | Genzyme Corporation | Adenovirus vector for gene therapy |
PT728214E (pt) | 1993-11-09 | 2004-11-30 | Ohio Med College | Linhas celulares estaveis capazes de expressar o gene de replicacao do virus adeno-associado |
US5658785A (en) | 1994-06-06 | 1997-08-19 | Children's Hospital, Inc. | Adeno-associated virus materials and methods |
US5559099A (en) | 1994-09-08 | 1996-09-24 | Genvec, Inc. | Penton base protein and methods of using same |
WO1996017947A1 (en) | 1994-12-06 | 1996-06-13 | Targeted Genetics Corporation | Packaging cell lines for generation of high titers of recombinant aav vectors |
US5770442A (en) | 1995-02-21 | 1998-06-23 | Cornell Research Foundation, Inc. | Chimeric adenoviral fiber protein and methods of using same |
ES2150832B1 (es) | 1996-06-12 | 2001-06-16 | Fichtel & Sachs Ag | Dispositivo de maniobra para la maniobra, en particular maniobra neumatica, de un embrague de friccion. |
AU5603998A (en) | 1996-12-18 | 1998-07-15 | Targeted Genetics Corporation | Recombinase-activatable AAV packaging cassettes for use in the production of AV vectors |
US5922315A (en) | 1997-01-24 | 1999-07-13 | Genetic Therapy, Inc. | Adenoviruses having altered hexon proteins |
EP1080218A1 (en) | 1998-05-27 | 2001-03-07 | University of Florida | Method of preparing recombinant adeno-associated virus compositions by using an iodixanol gradient |
EP1942192A1 (en) * | 2007-01-08 | 2008-07-09 | Heinrich-Pette-Institut für experimentelle Virologie und Immunologie | Use of a tailored recombinase for the treatment of retroviral infections |
US20100076057A1 (en) | 2008-09-23 | 2010-03-25 | Northwestern University | TARGET DNA INTERFERENCE WITH crRNA |
US9163289B2 (en) | 2010-08-27 | 2015-10-20 | Hanwha Techwin Co., Ltd. | Kit for detecting HIV-1 and method for detecting HIV-1 using the same |
ES2883590T3 (es) * | 2012-12-12 | 2021-12-09 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas |
-
2014
- 2014-03-25 JP JP2016506325A patent/JP6576904B2/ja active Active
- 2014-03-25 US US14/782,297 patent/US11274305B2/en active Active
- 2014-03-25 EP EP14779556.1A patent/EP2981612B1/en active Active
- 2014-03-25 WO PCT/US2014/031674 patent/WO2014165349A1/en active Application Filing
- 2014-03-25 CA CA2908253A patent/CA2908253C/en active Active
- 2014-03-25 ES ES14779556T patent/ES2747833T3/es active Active
-
2019
- 2019-08-21 JP JP2019151297A patent/JP6937802B2/ja active Active
-
2021
- 2021-08-27 JP JP2021139036A patent/JP7206338B2/ja active Active
-
2022
- 2022-02-01 US US17/590,560 patent/US20220154188A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6576904B2 (ja) * | 2013-04-04 | 2019-09-18 | トラスティーズ・オブ・ダートマス・カレッジ | HIV−1プロウイルスDNAのinvivo切除のための組成物及び方法 |
Non-Patent Citations (5)
Title |
---|
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2012, VOL.4, A006916, JPN6018006614, ISSN: 0004935773 * |
NATURE BIOTECHNOLOGY, MARCH 2013, VOL.31, P.230-232, JPN6018006609, ISSN: 0004935772 * |
NUCLEIC ACIDS RESEARCH, 2005, VOL.33, P.235-243, JPN6018006605, ISSN: 0004935770 * |
RNA GUIDED HUMAN GENE AND GENOME ENGONEERING AND RADICAL LIFE EXTENSION, DISEASE PREVENTION AND CURE, JPN6018006611, ISSN: 0004935774 * |
SCIENCE, 15 FEBRUARY 2013, VOL.339, P.823-826, JPN6018006607, ISSN: 0004935771 * |
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CA2908253C (en) | 2024-01-09 |
ES2747833T3 (es) | 2020-03-11 |
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JP6937802B2 (ja) | 2021-09-22 |
EP2981612A4 (en) | 2017-01-18 |
EP2981612A1 (en) | 2016-02-10 |
JP7206338B2 (ja) | 2023-01-17 |
CA2908253A1 (en) | 2014-10-09 |
US11274305B2 (en) | 2022-03-15 |
WO2014165349A1 (en) | 2014-10-09 |
JP2019198329A (ja) | 2019-11-21 |
JP2016514479A (ja) | 2016-05-23 |
US20160040165A1 (en) | 2016-02-11 |
US20220154188A1 (en) | 2022-05-19 |
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