CA3203876A1 - Variants d'editeur primaire, constructions et procedes pour ameliorer l'efficacite et la precision d'une edition primaire - Google Patents

Variants d'editeur primaire, constructions et procedes pour ameliorer l'efficacite et la precision d'une edition primaire 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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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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Publication of CA3203876A1 publication Critical patent/CA3203876A1/fr
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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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding 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
    • C12N15/10—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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1241—Nucleotidyltransferases (2.7.7)
    • C12N9/1276—RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase
    • 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
    • C12Y—ENZYMES
    • C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/07—Nucleotidyltransferases (2.7.7)
    • C12Y207/07049—RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • 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
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3519—Fusion 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)

Abstract

La présente invention concerne des compositions et des procédés d'édition primaire avec une efficacité d'édition améliorée et/ou une moindre formation d'indel par inhibition de la voie de réparation de mésappariement d'ADN tout en réalisant une édition primaire d'un site cible. En conséquence, la présente invention concerne un procédé d'édition d'une molécule d'acide nucléique par édition primaire qui implique la mise en contact d'une molécule d'acide nucléique avec un éditeur primaire, un ARNpeg, et un inhibiteur de la voie de réparation de mésappariement d'ADN, ce qui permet d'installer une ou plusieurs modifications sur la molécule d'acide nucléique au niveau d'un site cible avec une efficacité d'édition accrue et/ou une moindre formation d'indel. La présente invention concerne en outre des polynucléotides pour l'édition d'un site cible d'ADN par édition primaire comprenant une séquence d'acide nucléique codant un napDNAbp, une polymérase, et un inhibiteur de la voie de réparation de mésappariement d'ADN, le napDNAbp et la polymérase étant capables en présence d'un ARNpeg d'installer une ou plusieurs modifications dans le site cible d'ADN avec une efficacité d'édition accrue et/ou une moindre formation d'indel. La divulgation concerne en outre des vecteurs, des cellules et des kits comprenant les compositions et les polynucléotides de l'invention. La présente invention concerne également des compositions et des procédés d'édition primaire avec une efficacité d'édition améliorée et/ou une moindre formation d'indel avec des protéines de fusion d'éditeur primaire modifiées. La divulgation concerne en outre des vecteurs, des cellules et des kits comprenant les compositions et les polynucléotides de la divulgation.
CA3203876A 2021-01-11 2022-01-11 Variants d'editeur primaire, constructions et procedes pour ameliorer l'efficacite et la precision d'une edition primaire Pending CA3203876A1 (fr)

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 (fr) 2021-01-11 2022-01-11 Variants d'éditeur primaire, constructions et procédés pour améliorer l'efficacité et la précision d'une édition primaire

Publications (1)

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

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CA3203876A Pending CA3203876A1 (fr) 2021-01-11 2022-01-11 Variants d'editeur primaire, constructions et procedes pour ameliorer l'efficacite et la precision d'une edition primaire

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EP (1) EP4274894A2 (fr)
JP (1) JP2024503437A (fr)
AU (1) AU2022206476A1 (fr)
CA (1) CA3203876A1 (fr)
WO (1) WO2022150790A2 (fr)

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