CA3153624A1 - Nucleobase editors and methods of using same - Google Patents

Nucleobase editors and methods of using same Download PDF

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Publication number
CA3153624A1
CA3153624A1 CA3153624A CA3153624A CA3153624A1 CA 3153624 A1 CA3153624 A1 CA 3153624A1 CA 3153624 A CA3153624 A CA 3153624A CA 3153624 A CA3153624 A CA 3153624A CA 3153624 A1 CA3153624 A1 CA 3153624A1
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CA
Canada
Prior art keywords
adenosine deaminase
mutations
fusion protein
cas9
domain
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
CA3153624A
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English (en)
French (fr)
Inventor
Nicole GAUDELLI
Michael Packer
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
Original Assignee
Beam Therapeutics Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from PCT/US2020/018195 external-priority patent/WO2020168135A1/en
Application filed by Beam Therapeutics Inc filed Critical Beam Therapeutics Inc
Publication of CA3153624A1 publication Critical patent/CA3153624A1/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
    • 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)
    • 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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • 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
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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]

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
CA3153624A 2019-09-09 2020-09-09 Nucleobase editors and methods of using same Pending CA3153624A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201962897777P 2019-09-09 2019-09-09
US62/897,777 2019-09-09
USPCT/US2020/018195 2020-02-13
PCT/US2020/018195 WO2020168135A1 (en) 2019-02-13 2020-02-13 Compositions and methods for treating alpha-1 antitrypsin deficiency
PCT/US2020/049975 WO2021050571A1 (en) 2019-09-09 2020-09-09 Novel nucleobase editors and methods of using same

Publications (1)

Publication Number Publication Date
CA3153624A1 true CA3153624A1 (en) 2021-03-18

Family

ID=74867196

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3153624A Pending CA3153624A1 (en) 2019-09-09 2020-09-09 Nucleobase editors and methods of using same

Country Status (8)

Country Link
US (1) US20230075877A1 (enExample)
EP (1) EP4028026A4 (enExample)
JP (2) JP7717684B2 (enExample)
KR (1) KR20220076467A (enExample)
CN (1) CN114667149A (enExample)
AU (1) AU2020344547A1 (enExample)
CA (1) CA3153624A1 (enExample)
WO (1) WO2021050571A1 (enExample)

Families Citing this family (38)

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WO2019217942A1 (en) 2018-05-11 2019-11-14 Beam Therapeutics Inc. Methods of substituting pathogenic amino acids using programmable base editor systems
KR20210055733A (ko) 2018-09-07 2021-05-17 빔 테라퓨틱스, 인크. 핵염기 편집 시스템을 전달하기 위한 조성물 및 방법
EP3850088A4 (en) 2018-09-07 2023-07-19 Beam Therapeutics, Inc. Compositions and methods for improving base editing
JP7646552B2 (ja) 2019-01-31 2025-03-17 ビーム セラピューティクス インク． 低減された非標的脱アミノ化を有する核酸塩基エディターおよび核酸塩基エディターの特徴づけのためのアッセイ
WO2020168135A1 (en) * 2019-02-13 2020-08-20 Beam Therapeutics Inc. Compositions and methods for treating alpha-1 antitrypsin deficiency
US12600971B2 (en) 2019-02-13 2026-04-14 Beam Therapeutics Inc. Modified immune cells having adenosine deaminase base editors for modifying a nucleobase in a target sequence
CN114096666B (zh) 2019-02-13 2025-03-18 比姆医疗股份有限公司 治疗血红素病变的组合物和方法
AU2020344547A1 (en) * 2019-09-09 2022-03-24 Beam Therapeutics Inc. Novel nucleobase editors and methods of using same
US12594301B2 (en) 2019-09-27 2026-04-07 Beam Therapeutics Inc. Compositions and methods for treatment of liquid cancers
AU2021347359A1 (en) 2020-09-25 2023-05-18 Beam Therapeutics Inc. Fratricide resistant modified immune cells and methods of using the same
BR112023019539A2 (pt) * 2021-03-26 2023-12-05 Beam Therapeutics Inc Variantes de adenosina desaminase e usos das mesmas
WO2022240858A1 (en) 2021-05-10 2022-11-17 Mammoth Biosciences, Inc. Effector proteins and methods of use
KR20240012377A (ko) * 2021-05-28 2024-01-29 빔 테라퓨틱스, 인크. 염기 편집기의 자기-불활성화용 조성물 및 방법
EP4363568A4 (en) * 2021-06-29 2025-12-03 Council Scient Ind Res MODIFIED FNCAS9 AND ITS USES
EP4396207A4 (en) * 2021-09-03 2025-07-16 Univ Chicago POLYPEPTIDES AND METHODS FOR MODIFYING NUCLEIC ACIDS
EP4399307A4 (en) * 2021-09-08 2026-01-21 Flagship Pioneering Innovations Vi Llc HBB COMPOSITIONS AND MODULATION METHODS
EP4409000A1 (en) 2021-09-28 2024-08-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Base editing approaches for the treatment of beta-hemoglobinopathies
WO2023099591A1 (en) 2021-12-01 2023-06-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for increasing fetal hemoglobin content by editing the +55-kb region of the erythroid-specific bcl11a enhancer
WO2023141590A2 (en) 2022-01-21 2023-07-27 Mammoth Biosciences, Inc. Effector proteins and methods of use
WO2023144104A1 (en) 2022-01-25 2023-08-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Base editing approaches for the treatment of βeta-thalassemia
WO2023196802A1 (en) 2022-04-04 2023-10-12 The Broad Institute, Inc. Cas9 variants having non-canonical pam specificities and uses thereof
CN120456933A (zh) 2022-04-28 2025-08-08 布罗德研究所股份有限公司 编码碱基编辑器的aav载体及其用途
WO2023217888A1 (en) 2022-05-10 2023-11-16 Institut National de la Santé et de la Recherche Médicale Base editing approaches for correcting the cd39 (cag>tag) mutation in patients suffering from βeta-thalassemia
JP2025517657A (ja) 2022-05-10 2025-06-10 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル シンシチン－１融合タンパク質及び標的細胞へのカーゴ送達のためのその使用
EP4544035A4 (en) * 2022-06-27 2026-06-24 Beam Therapeutics Inc ADENOSINE DEAMINASE BASIC EDITORS AND THEIR METHODS OF USE
WO2024018056A1 (en) 2022-07-22 2024-01-25 Institut National de la Santé et de la Recherche Médicale Base editing approaches for correcting the ivs2-1 (g>a) mutation in patients suffering from βeta-thalassemia
CN115820691B (zh) * 2022-07-25 2023-08-22 安徽农业大学 一种基于LbCpf1变体的水稻碱基编辑系统和应用
AU2023325079A1 (en) 2022-08-16 2025-02-13 President And Fellows Of Harvard College Evolved cytosine deaminases and methods of editing dna using same
CN115975986B (zh) * 2022-08-22 2023-08-08 山东舜丰生物科技有限公司 突变的Cas12j蛋白及其应用
WO2024063273A1 (en) * 2022-09-23 2024-03-28 Institute For Basic Science Novel adenine deaminase variants and a method for base editing using the same
WO2024165484A1 (en) 2023-02-06 2024-08-15 Institut National de la Santé et de la Recherche Médicale Enrichment of genetically modified hematopoietic stem cells through multiplex base editing
WO2024230760A1 (zh) * 2023-05-09 2024-11-14 北京齐禾生科生物科技有限公司 一种可作用于dna的腺苷脱氨酶及其应用
CN117965505A (zh) * 2023-06-28 2024-05-03 微光基因(苏州)有限公司 工程化的腺苷脱氨酶及碱基编辑器
KR20260044217A (ko) 2023-07-25 2026-04-01 플래그쉽 파이어니어링 이노베이션스 Vii, 엘엘씨 Cas 엔도뉴클레아제 및 관련 방법
EP4777618A1 (en) * 2023-09-15 2026-07-22 Beam Therapeutics Inc. Compositions and methods for base editing a phenylalanine hydroxylase polynucleotide
WO2025072331A1 (en) 2023-09-26 2025-04-03 Flagship Pioneering Innovations Vii, Llc Cas nucleases and related methods
WO2025117877A2 (en) 2023-12-01 2025-06-05 Flagship Pioneering Innovations Vii, Llc Cas nucleases and related methods
CN120536418A (zh) * 2024-02-26 2025-08-26 尧唐(上海)生物科技有限公司 一种脱氨酶变体、包含其的碱基编辑器及其应用

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AU2015332533B2 (en) * 2014-10-14 2018-08-30 Halozyme, Inc. Compositions of adenosine deaminase-2 (ADA2), variants thereof and methods of using same
WO2018027078A1 (en) * 2016-08-03 2018-02-08 President And Fellows Of Harard College Adenosine nucleobase editors and uses thereof
US11242542B2 (en) * 2016-10-07 2022-02-08 Integrated Dna Technologies, Inc. S. pyogenes Cas9 mutant genes and polypeptides encoded by same
KR20240007715A (ko) * 2016-10-14 2024-01-16 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 핵염기 에디터의 aav 전달
US11180778B2 (en) * 2016-11-11 2021-11-23 The Regents Of The University Of California Variant RNA-guided polypeptides and methods of use
CA3082251A1 (en) * 2017-10-16 2019-04-25 The Broad Institute, Inc. Uses of adenosine base editors
AR114014A1 (es) * 2017-12-22 2020-07-08 Inst Genetics & Developmental Biology Cas Sistema de edición de bases y método basado en proteína cpf1
CN109295186B (zh) * 2018-09-30 2023-10-03 中山大学 一种基于全基因组测序检测腺嘌呤单碱基编辑系统脱靶效应的方法及其在基因编辑中的应用
AU2020344547A1 (en) * 2019-09-09 2022-03-24 Beam Therapeutics Inc. Novel nucleobase editors and methods of using same

Also Published As

Publication number Publication date
KR20220076467A (ko) 2022-06-08
JP7717684B2 (ja) 2025-08-04
EP4028026A4 (en) 2023-09-06
JP2025170240A (ja) 2025-11-18
EP4028026A1 (en) 2022-07-20
US20230075877A1 (en) 2023-03-09
WO2021050571A1 (en) 2021-03-18
AU2020344547A1 (en) 2022-03-24
JP2022546608A (ja) 2022-11-04
CN114667149A (zh) 2022-06-24

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