CA3127494A1 - Nucleobase editors having reduced off-target deamination and methods of using same to modify a nucleobase target sequence - Google Patents

Nucleobase editors having reduced off-target deamination and methods of using same to modify a nucleobase target sequence Download PDF

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Publication number
CA3127494A1
CA3127494A1 CA3127494A CA3127494A CA3127494A1 CA 3127494 A1 CA3127494 A1 CA 3127494A1 CA 3127494 A CA3127494 A CA 3127494A CA 3127494 A CA3127494 A CA 3127494A CA 3127494 A1 CA3127494 A1 CA 3127494A1
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CA
Canada
Prior art keywords
cytidine
deaminase
fusion protein
base editor
cytidine deaminase
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CA3127494A
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English (en)
French (fr)
Inventor
Nicole GAUDELLI
Yi Yu
Ian SLAYMAKER
Jason Michael GEHRKE
Seung-Joo Lee
David A. BORN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beam Therapeutics Inc
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Beam Therapeutics Inc
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Filing date
Publication date
Application filed by Beam Therapeutics Inc filed Critical Beam Therapeutics Inc
Publication of CA3127494A1 publication Critical patent/CA3127494A1/en
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2497—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing N- glycosyl compounds (3.2.2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
    • C12Y305/04005—Cytidine deaminase (3.5.4.5)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
    • C12Y305/04004—Adenosine deaminase (3.5.4.4)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Mycology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
CA3127494A 2019-01-31 2020-01-31 Nucleobase editors having reduced off-target deamination and methods of using same to modify a nucleobase target sequence Pending CA3127494A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201962799702P 2019-01-31 2019-01-31
US62/799,702 2019-01-31
US201962835456P 2019-04-17 2019-04-17
US62/835,456 2019-04-17
US201962941569P 2019-11-27 2019-11-27
US62/941,569 2019-11-27
PCT/US2020/016288 WO2020160517A1 (en) 2019-01-31 2020-01-31 Nucleobase editors having reduced off-target deamination and methods of using same to modify a nucleobase target sequence

Publications (1)

Publication Number Publication Date
CA3127494A1 true CA3127494A1 (en) 2020-08-06

Family

ID=71842357

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3127494A Pending CA3127494A1 (en) 2019-01-31 2020-01-31 Nucleobase editors having reduced off-target deamination and methods of using same to modify a nucleobase target sequence

Country Status (8)

Country Link
US (1) US20220136012A1 (https=)
EP (1) EP3918077A4 (https=)
JP (2) JP7600122B2 (https=)
KR (1) KR20210124280A (https=)
CN (2) CN114072509B (https=)
AU (1) AU2020216484A1 (https=)
CA (1) CA3127494A1 (https=)
WO (1) WO2020160517A1 (https=)

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US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
EP3592853A1 (en) 2017-03-09 2020-01-15 President and Fellows of Harvard College Suppression of pain by gene editing
EP3676376B1 (en) 2017-08-30 2025-01-15 President and Fellows of Harvard College High efficiency base editors comprising gam
US12406749B2 (en) 2017-12-15 2025-09-02 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
AU2019265019B2 (en) 2018-05-11 2025-11-06 Beam Therapeutics Inc. Methods of substituting pathogenic amino acids using programmable base editor systems
US12157760B2 (en) 2018-05-23 2024-12-03 The Broad Institute, Inc. Base editors and uses thereof
US12522807B2 (en) 2018-07-09 2026-01-13 The Broad Institute, Inc. RNA programmable epigenetic RNA modifiers and uses thereof
EP3847254A4 (en) 2018-09-07 2022-08-10 Beam Therapeutics Inc. COMPOSITIONS AND METHODS FOR DELIVERING A NUCLEOBASE EDITING SYSTEM
WO2020051562A2 (en) 2018-09-07 2020-03-12 Beam Therapeutics Inc. Compositions and methods for improving base editing
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
AU2020215730A1 (en) 2019-01-31 2021-07-29 Beam Therapeutics Inc. Nucleobase editors having reduced non-target deamination and assays for characterizing nucleobase editors
CN120174005A (zh) 2019-02-13 2025-06-20 比姆医疗股份有限公司 具有用于修饰靶标序列中核碱基的腺苷脱氨酶碱基编辑器的经修饰的免疫细胞
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
EP4034138A4 (en) 2019-09-27 2024-07-31 Beam Therapeutics, Inc. COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIQUID CANCERS
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
US12416001B2 (en) * 2020-02-14 2025-09-16 Ohio State Innovation Foundation Nucleobase editors and methods of use thereof
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
CA3196831A1 (en) 2020-09-25 2022-03-31 Beam Therapeutics Inc. Fratricide resistant modified immune cells and methods of using the same
EP4313118A4 (en) * 2021-03-26 2025-06-18 Beam Therapeutics Inc. ADENOSINE DEAMINASE VARIANTS AND THEIR USES
KR20240007651A (ko) * 2021-04-16 2024-01-16 빔 테라퓨틱스, 인크. 간세포의 유전적 변형
WO2022261509A1 (en) * 2021-06-11 2022-12-15 The Broad Institute, Inc. Improved cytosine to guanine base editors
US20240352439A1 (en) * 2021-09-03 2024-10-24 The University Of Chicago Polypeptides and methods for modifying nucleic acids
WO2023086953A1 (en) * 2021-11-11 2023-05-19 Beam Therapeutics Inc. Compositions and methods for the treatment of hereditary angioedema (hae)
CN114686456B (zh) * 2022-05-10 2023-02-17 中山大学 基于双分子脱氨酶互补的碱基编辑系统及其应用
EP4540378A1 (en) * 2022-06-20 2025-04-23 CRISPR Therapeutics AG Base editing proteins and uses thereof
EP4605542A1 (en) * 2022-10-19 2025-08-27 DNA Script Methods and products for removal of uracil containing polynucleotides
CN117384885B (zh) 2022-12-15 2025-06-10 中国科学院遗传与发育生物学研究所 一种碱基编辑器及其应用
CN118475691B (zh) * 2023-02-28 2025-07-22 锐正基因(苏州)有限公司 用于碱基编辑的脱氨酶
WO2024240223A1 (en) 2023-05-24 2024-11-28 Accuredit Therapeutics (Suzhou) Co., Ltd. Deaminases and variants thereof for use in base editing
CN117210445A (zh) * 2023-08-29 2023-12-12 苏州湃芮生物科技有限公司 一种基于rna特异性脱氨酶突变体及其应用
CN120813698A (zh) * 2023-09-22 2025-10-17 北京大学现代农业研究院 改进的基因组编辑方法
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KR20240116572A (ko) * 2017-03-23 2024-07-29 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제
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Also Published As

Publication number Publication date
CN120400115A (zh) 2025-08-01
JP2022521460A (ja) 2022-04-08
KR20210124280A (ko) 2021-10-14
WO2020160517A1 (en) 2020-08-06
EP3918077A1 (en) 2021-12-08
EP3918077A4 (en) 2023-03-29
AU2020216484A1 (en) 2021-07-29
CN114072509A (zh) 2022-02-18
JP2025041661A (ja) 2025-03-26
JP7779988B2 (ja) 2025-12-03
JP7600122B2 (ja) 2024-12-16
CN114072509B (zh) 2025-04-15
US20220136012A1 (en) 2022-05-05

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