CA3203876A1 - Prime editor variants, constructs, and methods for enhancing prime editing efficiency and precision - Google Patents

Prime editor variants, constructs, and methods for enhancing prime editing efficiency and precision Download PDF

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Publication number
CA3203876A1
CA3203876A1 CA3203876A CA3203876A CA3203876A1 CA 3203876 A1 CA3203876 A1 CA 3203876A1 CA 3203876 A CA3203876 A CA 3203876A CA 3203876 A CA3203876 A CA 3203876A CA 3203876 A1 CA3203876 A1 CA 3203876A1
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fold
seq
dna
amino acid
basepair
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CA3203876A
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English (en)
French (fr)
Inventor
David R. Liu
Peter J. Chen
Brittany ADAMSON
Jeffrey HUSSMANN
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Princeton University
Broad Institute Inc
Harvard University
University of California San Diego UCSD
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Princeton University
Broad Institute Inc
Harvard University
University of California San Diego UCSD
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Application filed by Princeton University, Broad Institute Inc, Harvard University, University of California San Diego UCSD filed Critical Princeton University
Publication of CA3203876A1 publication Critical patent/CA3203876A1/en
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111General methods applicable to biologically active non-coding nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102Mutagenizing nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10Transferases (2.)
    • C12N9/12Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1241Nucleotidyltransferases (2.7.7)
    • C12N9/1276RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/16Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y207/00Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/07Nucleotidyltransferases (2.7.7)
    • C12Y207/07049RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y301/00Hydrolases acting on ester bonds (3.1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/20Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3519Fusion with another nucleic acid

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Steroid Compounds (AREA)
  • Document Processing Apparatus (AREA)
  • Steering-Linkage Mechanisms And Four-Wheel Steering (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
CA3203876A 2021-01-11 2022-01-11 Prime editor variants, constructs, and methods for enhancing prime editing efficiency and precision Pending CA3203876A1 (en)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
US202163136194P 2021-01-11 2021-01-11
US63/136,194 2021-01-11
US202163176202P 2021-04-16 2021-04-16
US202163176180P 2021-04-16 2021-04-16
US63/176,202 2021-04-16
US63/176,180 2021-04-16
US202163194865P 2021-05-28 2021-05-28
US202163194913P 2021-05-28 2021-05-28
US63/194,865 2021-05-28
US63/194,913 2021-05-28
US202163231230P 2021-08-09 2021-08-09
US63/231,230 2021-08-09
US202163255897P 2021-10-14 2021-10-14
US63/255,897 2021-10-14
PCT/US2022/012054 WO2022150790A2 (en) 2021-01-11 2022-01-11 Prime editor variants, constructs, and methods for enhancing prime editing efficiency and precision

Publications (1)

Publication Number Publication Date
CA3203876A1 true CA3203876A1 (en) 2022-07-14

Family

ID=80119064

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3203876A Pending CA3203876A1 (en) 2021-01-11 2022-01-11 Prime editor variants, constructs, and methods for enhancing prime editing efficiency and precision

Country Status (5)

Country Link
EP (1) EP4274894A2 (enExample)
JP (1) JP2024503437A (enExample)
AU (1) AU2022206476A1 (enExample)
CA (1) CA3203876A1 (enExample)
WO (1) WO2022150790A2 (enExample)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US10077453B2 (en) 2014-07-30 2018-09-18 President And Fellows Of Harvard College CAS9 proteins including ligand-dependent inteins
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
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
US12406749B2 (en) 2017-12-15 2025-09-02 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
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
WO2020191233A1 (en) 2019-03-19 2020-09-24 The Broad Institute, Inc. Methods and compositions for editing nucleotide sequences
US12473543B2 (en) 2019-04-17 2025-11-18 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
CN116209756A (zh) 2020-03-04 2023-06-02 旗舰先锋创新Vi有限责任公司 调控基因组的方法和组合物
KR20230053735A (ko) 2020-03-04 2023-04-21 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 게놈의 조정을 위한 개선된 방법 및 조성물
CA3231712A1 (en) 2021-09-08 2023-03-16 Flagship Pioneering Innovations Vi, Llc Pah-modulating compositions and methods
AU2022343268A1 (en) 2021-09-08 2024-03-28 Flagship Pioneering Innovations Vi, Llc Methods and compositions for modulating a genome
EP4437106A2 (en) * 2021-11-24 2024-10-02 Prime Medicine, Inc. Methods and compositions for inhibiting mismatch repair
WO2023108153A2 (en) 2021-12-10 2023-06-15 Flagship Pioneering Innovations Vi, Llc Cftr-modulating compositions and methods
CA3243220A1 (en) 2022-01-24 2023-07-27 LifeEDIT Therapeutics, Inc. RNA-GUIDED NUCLEASE AND ACTIVE FRAGMENTS, ASSOCIATED VARIANTS AND METHODS OF USE
CN116064512A (zh) * 2022-07-15 2023-05-05 山西大学 一种改进的引导编辑系统及其应用
WO2024026344A1 (en) * 2022-07-27 2024-02-01 Inscripta, Inc. Modulating cellular repair mechanisms for genomic editing
WO2024077267A1 (en) 2022-10-07 2024-04-11 The Broad Institute, Inc. Prime editing methods and compositions for treating triplet repeat disorders
WO2024178144A1 (en) * 2023-02-22 2024-08-29 Prime Medicine, Inc. Methods and compositions for editing nucleotide sequences
EP4677117A1 (en) * 2023-03-09 2026-01-14 The Regents of the University of California High throughput prime editing screens identify functional dna variants in the human genome
WO2024192141A1 (en) 2023-03-13 2024-09-19 Dana-Farber Cancer Institute, Inc. Treatment of cancers having a drug-resistant mesenchymal cell state
WO2024197185A1 (en) 2023-03-21 2024-09-26 The Broad Institute, Inc. Methods and compositions for dissecting organelle physiology
WO2024206125A1 (en) * 2023-03-24 2024-10-03 The Broad Institute, Inc. Use of prime editing for treating sickle cell disease
WO2024215712A2 (en) * 2023-04-11 2024-10-17 University Of Washington Methods for identifying epigenetic factors influencing gene editing and modulating gene editing outcome via epigenetic modulation
CN118792282A (zh) * 2023-04-13 2024-10-18 深圳大学 Un1Cas12f1突变体及其应用
WO2024226838A2 (en) 2023-04-25 2024-10-31 The Brigham And Women's Hospital, Inc. Treatment of autoimmune diseases having a pathogenic t cell state
WO2024243415A1 (en) 2023-05-23 2024-11-28 The Broad Institute, Inc. Evolved and engineered prime editors with improved editing efficiency
WO2025017030A1 (en) * 2023-07-17 2025-01-23 Institut National de la Santé et de la Recherche Médicale Prime editing of the -200 region in the hbg1 and/or hbg2 promoter for increasing fetal hemoglobin content in a eukaryotic cell
WO2025017033A1 (en) * 2023-07-17 2025-01-23 Institut National de la Santé et de la Recherche Médicale Prime editing of the -115 region in the hbg1 and/or hbg2 promoter for increasing fetal hemoglobin content in a eukaryotic cell
AU2024301706A1 (en) 2023-07-21 2026-02-05 Crispr Therapeutics Ag Modulating expression of alas1 (5'-aminolevulinate synthase 1) gene
WO2025049563A1 (en) * 2023-08-28 2025-03-06 University Of Florida Research Foundation, Inc. A programmable gene correction technology using cas-polymerase constructs
WO2025049788A1 (en) 2023-08-29 2025-03-06 The Broad Institute, Inc. Optical genetic screens of intracellular and intercellular transcriptional circuits with perturb-fish
WO2025049928A1 (en) * 2023-09-01 2025-03-06 Arbor Biotechnologies, Inc. Reverse transcription-mediated gene editing systems and uses thereof
WO2025096936A2 (en) 2023-11-03 2025-05-08 The Broad Institute, Inc. Use of prime editing in correcting mutations in cdkl5
WO2025096916A1 (en) 2023-11-03 2025-05-08 The Broad Institute, Inc. Multi-site editing in living cells
WO2025129158A1 (en) 2023-12-15 2025-06-19 The Broad Institute, Inc. Engineered arc delivery vesicles and uses thereof
CN118185999B (zh) * 2024-01-03 2025-11-14 福州大学 一种PE-NRGEER mRNA体外转录模板质粒、PE碱基编辑器及其应用
WO2025151814A1 (en) 2024-01-10 2025-07-17 The Broad Institute, Inc. Use of prime editing in correcting mutations in cftr
WO2025217616A1 (en) 2024-04-12 2025-10-16 The Broad Institute, Inc. Prime editing and base editing of the atp1a3 gene for the treatment of alternating hemiplegia of childhood
WO2026015480A1 (en) * 2024-07-08 2026-01-15 Integrated Dna Technologies, Inc. Cas9 and reverse transcriptase mutants with improved activity in prime editing applications
WO2026069163A1 (en) 2024-09-25 2026-04-02 Crispr Therapeutics Ag Differentiation method for producing immature beta cells

Family Cites Families (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4217344A (en) 1976-06-23 1980-08-12 L'oreal Compositions containing aqueous dispersions of lipid spheres
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4186183A (en) 1978-03-29 1980-01-29 The United States Of America As Represented By The Secretary Of The Army Liposome carriers in chemotherapy of leishmaniasis
US4261975A (en) 1979-09-19 1981-04-14 Merck & Co., Inc. Viral liposome particle
US4663290A (en) 1982-01-21 1987-05-05 Molecular Genetics, Inc. Production of reverse transcriptase
US4485054A (en) 1982-10-04 1984-11-27 Lipoderm Pharmaceuticals Limited Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV)
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US5049386A (en) 1985-01-07 1991-09-17 Syntex (U.S.A.) Inc. N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4946787A (en) 1985-01-07 1990-08-07 Syntex (U.S.A.) Inc. N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4774085A (en) 1985-07-09 1988-09-27 501 Board of Regents, Univ. of Texas Pharmaceutical administration systems containing a mixture of immunomodulators
US5374553A (en) 1986-08-22 1994-12-20 Hoffmann-La Roche Inc. DNA encoding a thermostable nucleic acid polymerase enzyme from thermotoga maritima
US4889818A (en) 1986-08-22 1989-12-26 Cetus Corporation Purified thermostable enzyme
US5079352A (en) 1986-08-22 1992-01-07 Cetus Corporation Purified thermostable enzyme
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5244797B1 (en) 1988-01-13 1998-08-25 Life Technologies Inc Cloned genes encoding reverse transcriptase lacking rnase h activity
FR2632821B1 (fr) 1988-06-22 1990-11-16 Inst Kriobiologii Procede de conservation a basse temperature des embryons
US5047342A (en) 1989-08-10 1991-09-10 Life Technologies, Inc. Cloning and expression of T5 DNA polymerase
US5270179A (en) 1989-08-10 1993-12-14 Life Technologies, Inc. Cloning and expression of T5 DNA polymerase reduced in 3'- to-5' exonuclease activity
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
WO1991017424A1 (en) 1990-05-03 1991-11-14 Vical, Inc. Intracellular delivery of biologically active substances by means of self-assembling lipid complexes
JP2709311B2 (ja) 1990-09-28 1998-02-04 エフ.ホフマン−ラ ロシュ アクチェンゲゼルシャフト 熱安定性dnaポリメラーゼの5→3′のエキソヌクレアーゼ突然変異
AU8906091A (en) 1990-10-05 1992-04-28 Wayne M. Barnes Thermostable dna polymerase
US5436149A (en) 1993-02-19 1995-07-25 Barnes; Wayne M. Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension
US5512462A (en) 1994-02-25 1996-04-30 Hoffmann-La Roche Inc. Methods and reagents for the polymerase chain reaction amplification of long DNA sequences
US5912155A (en) 1994-09-30 1999-06-15 Life Technologies, Inc. Cloned DNA polymerases from Thermotoga neapolitana
US5614365A (en) 1994-10-17 1997-03-25 President & Fellow Of Harvard College DNA polymerase having modified nucleotide binding site for DNA sequencing
US5773258A (en) 1995-08-25 1998-06-30 Roche Molecular Systems, Inc. Nucleic acid amplification using a reversibly inactivated thermostable enzyme
US6183998B1 (en) 1998-05-29 2001-02-06 Qiagen Gmbh Max-Volmer-Strasse 4 Method for reversible modification of thermostable enzymes
US6534261B1 (en) 1999-01-12 2003-03-18 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
GB9920194D0 (en) 1999-08-27 1999-10-27 Advanced Biotech Ltd A heat-stable thermostable DNA polymerase for use in nucleic acid amplification
EP1235914A2 (en) 1999-11-24 2002-09-04 Joseph Rosenecker Polypeptides comprising multimers of nuclear localization signals or of protein transduction domains and their use for transferring molecules into cells
US8178291B2 (en) 2005-02-18 2012-05-15 Monogram Biosciences, Inc. Methods and compositions for determining hypersusceptibility of HIV-1 to non-nucleoside reverse transcriptase inhibitors
US9783791B2 (en) 2005-08-10 2017-10-10 Agilent Technologies, Inc. Mutant reverse transcriptase and methods of use
CN101668848B (zh) 2007-04-26 2014-10-22 雷蒙特亚特特拉维夫大学有限公司 来自口腔粘膜的多能自体干细胞和使用方法
WO2010028347A2 (en) 2008-09-05 2010-03-11 President & Fellows Of Harvard College Continuous directed evolution of proteins and nucleic acids
US10113156B2 (en) 2009-03-04 2018-10-30 Board Of Regents, The University Of Texas System Stabilized reverse transcriptase fusion proteins
US8889394B2 (en) 2009-09-07 2014-11-18 Empire Technology Development Llc Multiple domain proteins
WO2011072246A2 (en) 2009-12-10 2011-06-16 Regents Of The University Of Minnesota Tal effector-mediated dna modification
WO2012054727A1 (en) 2010-10-22 2012-04-26 Bio-Rad Laboratories, Inc. Reverse transcriptase mixtures with improved storage stability
CA2825370A1 (en) 2010-12-22 2012-06-28 President And Fellows Of Harvard College Continuous directed evolution
KR102096534B1 (ko) 2011-09-28 2020-04-03 에라 바이오테크, 에스.에이. 분할된 인테인 및 그의 이용
EP3431497B1 (en) 2012-06-27 2022-07-27 The Trustees of Princeton University Split inteins, conjugates and uses thereof
US9181535B2 (en) 2012-09-24 2015-11-10 The Chinese University Of Hong Kong Transcription activator-like effector nucleases (TALENs)
DK2904101T3 (da) 2012-10-03 2019-08-12 Agrivida Inc Intein-modificerede proteaser, fremstilling deraf og industrielle anvendelser
JO3470B1 (ar) 2012-10-08 2020-07-05 Merck Sharp & Dohme مشتقات 5- فينوكسي-3h-بيريميدين-4-أون واستخدامها كمثبطات ناسخ عكسي ل hiv
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
WO2015134121A2 (en) 2014-01-20 2015-09-11 President And Fellows Of Harvard College Negative selection and stringency modulation in continuous evolution systems
CN107075491B (zh) 2014-10-28 2021-07-06 谷万达公司 用于稳定反式剪接的内含肽修饰的蛋白酶的方法和组合物
WO2016168631A1 (en) 2015-04-17 2016-10-20 President And Fellows Of Harvard College Vector-based mutagenesis system
US9580698B1 (en) 2016-09-23 2017-02-28 New England Biolabs, Inc. Mutant reverse transcriptase
KR20210121092A (ko) * 2019-01-29 2021-10-07 유니버시티 오브 워싱턴 유전자 편집 방법
WO2020180975A1 (en) * 2019-03-04 2020-09-10 President And Fellows Of Harvard College Highly multiplexed base editing
WO2020181202A1 (en) * 2019-03-06 2020-09-10 The Broad Institute, Inc. A:t to t:a base editing through adenine deamination and oxidation
WO2020181193A1 (en) * 2019-03-06 2020-09-10 The Broad Institute, Inc. T:a to a:t base editing through adenosine methylation
WO2020181180A1 (en) * 2019-03-06 2020-09-10 The Broad Institute, Inc. A:t to c:g base editors and uses thereof
WO2020181195A1 (en) * 2019-03-06 2020-09-10 The Broad Institute, Inc. T:a to a:t base editing through adenine excision
WO2020181178A1 (en) * 2019-03-06 2020-09-10 The Broad Institute, Inc. T:a to a:t base editing through thymine alkylation
WO2020191233A1 (en) * 2019-03-19 2020-09-24 The Broad Institute, Inc. Methods and compositions for editing nucleotide sequences
US12473543B2 (en) * 2019-04-17 2025-11-18 The Broad Institute, Inc. Adenine base editors with reduced off-target effects

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WO2022150790A2 (en) 2022-07-14
JP2024503437A (ja) 2024-01-25
WO2022150790A3 (en) 2022-08-11
EP4274894A2 (en) 2023-11-15
AU2022206476A1 (en) 2023-07-20

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