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
    • 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]
    • 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)

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)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (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 (https=)
EP (1) EP4028026A4 (https=)
JP (2) JP7717684B2 (https=)
KR (1) KR20220076467A (https=)
CN (1) CN114667149A (https=)
AU (1) AU2020344547A1 (https=)
CA (1) CA3153624A1 (https=)
WO (1) WO2021050571A1 (https=)

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AU2019265019B2 (en) 2018-05-11 2025-11-06 Beam Therapeutics Inc. Methods of substituting pathogenic amino acids using programmable base editor systems
WO2020051562A2 (en) 2018-09-07 2020-03-12 Beam Therapeutics Inc. Compositions and methods for improving base editing
EP3847254A4 (en) 2018-09-07 2022-08-10 Beam Therapeutics Inc. COMPOSITIONS AND METHODS FOR DELIVERING A NUCLEOBASE EDITING SYSTEM
AU2020215730A1 (en) 2019-01-31 2021-07-29 Beam Therapeutics Inc. Nucleobase editors having reduced non-target deamination and assays for characterizing nucleobase editors
KR20210126680A (ko) * 2019-02-13 2021-10-20 빔 테라퓨틱스, 인크. 알파-1 항트립신 결핍증을 치료하기 위한 조성물 및 방법
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
CA3128755C (en) 2019-02-13 2024-06-04 Beam Therapeutics Inc. Compositions and methods for treating hemoglobinopathies
EP4034138A4 (en) 2019-09-27 2024-07-31 Beam Therapeutics, Inc. COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIQUID CANCERS
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
WO2022240858A1 (en) 2021-05-10 2022-11-17 Mammoth Biosciences, Inc. Effector proteins and methods of use
WO2023275892A1 (en) * 2021-06-29 2023-01-05 Council Of Scientific & Industrial Research Engineered fncas9 and uses thereof
US20240352439A1 (en) * 2021-09-03 2024-10-24 The University Of Chicago Polypeptides and methods for modifying nucleic acids
CA3231679A1 (en) * 2021-09-08 2023-03-16 Flagship Pioneering Innovations Vi, Llc Hbb-modulating compositions and 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
JP2025515503A (ja) 2022-04-28 2025-05-15 ザ ブロード インスティテュート，インコーポレーテッド 塩基エディタをコードするａａｖベクターおよびその使用
US20250223326A1 (en) 2022-05-10 2025-07-10 Institut National de la Santé et de la Recherche Médicale Syncitin-1 fusion proteins and uses thereof for cargo delivery into target cells
US20250241956A1 (en) 2022-05-10 2025-07-31 Institut National de la Santé et de la Recherche Médicale Base editing approaches for correcting the cd39 (cag>tag) mutation in patients suffering from beta-thalassemia
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
WO2024040083A1 (en) 2022-08-16 2024-02-22 The Broad Institute, Inc. Evolved cytosine deaminases and methods of editing dna using same
WO2024040874A1 (zh) * 2022-08-22 2024-02-29 山东舜丰生物科技有限公司 突变的Cas12j蛋白及其应用
KR20250075667A (ko) * 2022-09-23 2025-05-28 기초과학연구원 신규한 아데닌 탈아미노효소 변이체 및 이를 사용한 염기 교정 방법
JP2026506554A (ja) 2023-02-06 2026-02-25 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 多重塩基編集による遺伝子改変造血幹細胞の濃縮
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
WO2025059520A1 (en) * 2023-09-15 2025-03-20 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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KR20250107288A (ko) * 2017-10-16 2025-07-11 더 브로드 인스티튜트, 인코퍼레이티드 아데노신 염기 편집제의 용도
CN109957569B (zh) * 2017-12-22 2022-10-25 苏州齐禾生科生物科技有限公司 基于cpf1蛋白的碱基编辑系统和方法
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Also Published As

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

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