RU2021133626A - Варианты hsd17b13 и их применения - Google Patents

Варианты hsd17b13 и их применения Download PDF

Info

Publication number
RU2021133626A
RU2021133626A RU2021133626A RU2021133626A RU2021133626A RU 2021133626 A RU2021133626 A RU 2021133626A RU 2021133626 A RU2021133626 A RU 2021133626A RU 2021133626 A RU2021133626 A RU 2021133626A RU 2021133626 A RU2021133626 A RU 2021133626A
Authority
RU
Russia
Prior art keywords
guide rna
seq
cell
cas protein
hsd17b13 gene
Prior art date
Application number
RU2021133626A
Other languages
English (en)
Inventor
Нура С. АБУЛ-ХУСН
Омри ГОТТЕСМАН
Александер ЛИ
Сипин ЧЭН
Юйжун СИНЬ
Эвангелос ПЕФАНИС
Сюзанн ХАРТФОРД
Джеспер Громада
Фредерик Е. ДЬЮИ
Арис БАРАС
Алан ШУЛДИНЕР
Original Assignee
Регенерон Фармасьютикалз, Инк.
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
Application filed by Регенерон Фармасьютикалз, Инк. filed Critical Регенерон Фармасьютикалз, Инк.
Publication of RU2021133626A publication Critical patent/RU2021133626A/ru

Links

Classifications

    • 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
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
    • 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
    • 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
    • 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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • 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
    • C12N15/113—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
    • 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
    • C12N15/1137—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 against enzymes
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • 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
    • C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/067—Hepatocytes
    • 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 RNAses, DNAses
    • 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
    • C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • C12Q1/32—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving dehydrogenase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01051—3 (or 17)-Beta-hydroxysteroid dehydrogenase (1.1.1.51)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01062—17Beta-estradiol 17-dehydrogenase (1.1.1.62)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5067—Liver cells
    • 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
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
    • 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
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • 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 [CRISPRs]
    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/531—Stem-loop; Hairpin
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/34—Allele or polymorphism specific uses
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/24—Vectors characterised by the absence of particular element, e.g. selectable marker, viral origin of replication
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/118—Prognosis of disease development
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4703—Regulators; Modulating activity
    • G01N2333/4704—Inhibitors; Supressors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/08—Hepato-biliairy disorders other than hepatitis
    • G01N2800/085—Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin

Claims (55)

1. Способ модификации гена HSD17B13 в клетке, предусматривающий приведение генома клетки в контакт с:
(a) белком Cas; и
(b) гидовой РНК, содержащей часть РНК CRISPR (crRNA) и часть транс-активирующей РНК CRISPR (tracrRNA), причем гидовая РНК образует комплекс с белком Cas и нацелена на целевую для гидовой РНК последовательность в гене HSD17B13, причем целевая для гидовой РНК последовательность включает положение или находится в непосредственной близости от него, которое соответствует положению 12666 из SEQ ID NO: 2 при оптимальном выравнивании гена HSD17B13 с SEQ ID NO: 2, и
причем белок Cas расщепляет первую целевую для гидовой РНК последовательность с образованием целенаправленной генетической модификации в гене HSD17B13.
2. Способ по п. 1, предусматривающий что ген HSD17B13 не имеет тимина, вставленного между нуклеотидами, соответствующими положениям 12665 и 12666 из SEQ ID NO: 1 при оптимальном выравнивании гена HSD17B13 с SEQ ID NO: 1.
3. Способ по п. 1 или 2, предусматривающий, что:
(a) целевая для гидовой РНК последовательность содержит любую из SEQ ID NO: 226-239 и 264-268; и/или
(b) гидовая РНК содержит нацеливающий на ДНК сегмент, содержащий любую из SEQ ID NO: 1629-1642 и 1648-1652; и/или
(c) гидовая РНК содержит любую из SEQ ID NO: 706-719; 936-949; 1166-1179, 1396-1409, 725-729, 955-959, 1185-1189 и 1415-1419.
4. Способ по любому из предыдущих пунктов, предусматривающий, что целевая для гидовой РНК последовательность находится в пределах участка, соответствующего экзону 6 и/или интрону 6 из SEQ ID NO: 2 или находится в пределах участка, соответствующего экзону 6 и/или экзону 7 из SEQ ID NO: 2 при оптимальном выравнивании гена HSD17B13 с SEQ ID NO: 2.
5. Способ по любому из предыдущих пунктов, предусматривающий, что целевая для гидовой РНК последовательность находится в пределах приблизительно 1000, 500, 400, 300, 200, 100, 50, 45, 40, 35, 30, 25, 20, 15, 10 или 5 нуклеотидов от положения, соответствующего положению 12666 из SEQ ID NO: 2 при оптимальном выравнивании гена HSD17B13 с SEQ ID NO: 2.
6. Способ по любому из предыдущих пунктов, предусматривающий, что целевая для гидовой РНК последовательность включает положение, соответствующее положению 12666 из SEQ ID NO: 2 при оптимальном выравнивании гена HSD17B13 с SEQ ID NO: 2.
7. Способ по любому из предыдущих пунктов, дополнительно предусматривающий приведение генома клетки в контакт с одной или несколькими дополнительными гидовыми РНК, причем каждая из одной или нескольких дополнительных гидовых РНК образует комплекс с белком Cas и нацелена на целевую для дополнительной гидовой РНК последовательность в гене HSD17B13.
8. Способ по любому из предыдущих пунктов, предусматривающий, что способ приводит к разрушению донорного сплайс-сайта в интроне 6 гена HSD17B13.
9. Способ по любому из предыдущих пунктов, предусматривающий, что способ приводит к потере функции гена HSD17B13.
10. Способ по любому из предыдущих пунктов, предусматривающий, что целенаправленную генетическую модификацию получают путем репарации отщепленной целевой для гидовой РНК последовательности посредством негомологичного соединения концов.
11. Способ по любому из пп. 1-9, дополнительно предусматривающий введение в клетку экзогенной донорной последовательности, которая рекомбинирует с целевым геномным локусом в гене HSD17B13 с получением целенаправленной генетической модификации.
12. Способ по п. 11, предусматривающий, что репарация гена HSD17B13 с помощью экзогенной донорной последовательностью происходит посредством вставки, опосредованной негомологичным соединением концов.
13. Способ по п. 11, предусматривающий, что репарация гена HSD17B13 с помощью экзогенной донорной последовательности происходит посредством гомологичной репарации.
14. Способ по п. 13, предусматривающий, что экзогенная донорная последовательность содержит 5’ гомологичное плечо, которое гибридизируется с целевой последовательностью, находящейся 5’ от положения, соответствующего положению 12666 из SEQ ID NO: 2, и 3’ гомологичное плечо, которое гибридизируется с целевой последовательностью, находящейся 3’ от положения, соответствующего положению 12666 из SEQ ID NO: 2, причем экзогенная донорная последовательность рекомбинирует с геном HSD17B13.
15. Способ по п. 14, предусматривающий, что экзогенная донорная последовательность дополнительно содержит вставку нуклеиновой кислоты, фланкированную 5’ гомологичным плечом и 3’ гомологичным плечом.
16. Способ по п. 15, предусматривающий, что вставка нуклеиновой кислоты содержит тимин, и причем при рекомбинации экзогенной донорной последовательности с геном HSD17B13 тимин вставляется между нуклеотидами, соответствующими положениям 12665 и 12666 из SEQ ID NO: 1 при оптимальном выравнивании гена HSD17B13 с SEQ ID NO: 1.
17. Способ по любому из пп. 11-16, предусматривающий, что экзогенная донорная последовательность составляет от приблизительно 50 нуклеотидов до приблизительно 1 т. о. в длину.
18. Способ по п. 17, предусматривающий, что экзогенная донорная последовательность составляет от приблизительно 80 нуклеотидов до приблизительно 200 нуклеотидов в длину.
19. Способ по любому из пп. 11-18, предусматривающий, что экзогенная донорная последовательность является одноцепочечным олигодезоксинуклеотидом.
20. Способ по любому из предыдущих пунктов, предусматривающий, что белок Cas представляет собой белок Cas9.
21. Способ по любому из предыдущих пунктов, причем способ предусматривает введение в клетку:
(a) белка Cas или нуклеиновой кислоты, кодирующей такой белок Cas; и
(b) гидовой РНК или ДНК, кодирующей гидовую РНК.
22. Способ по п. 21, причем способ предусматривает введение в клетку нуклеиновой кислоты, кодирующей белок Cas.
23. Способ по п. 22, предусматривающий, что нуклеиновая кислота, кодирующая белок Cas, представляет собой ДНК.
24. Способ по п. 22, предусматривающий, что нуклеиновая кислота, кодирующая белок Cas, представляет собой РНК.
25. Способ по любому из пп. 21-24, причем способ предусматривает введение в клетку гидовой РНК в форме РНК.
26. Способ по любому из пп. 21-24, причем способ предусматривает введение в клетку ДНК, кодирующей гидовую РНК.
27. Способ по любому из пп. 21-26, предусматривающий, что белок Cas или нуклеиновую кислоту, кодирующую белок Cas, и/или гидовую РНК, или ДНК, кодирующую гидовую РНК, вводят в клетку посредством доставки, опосредованной липидными наночастицами.
28. Способ по любому из пп. 21-26, предусматривающий, что белок Cas или нуклеиновую кислоту, кодирующую белок Cas, и/или гидовую РНК, или ДНК, кодирующую гидовую РНК, вводят в клетку посредством аденоассоциированного вируса.
29. Способ по любому из предыдущих пунктов, предусматривающий, что гидовая РНК представляет собой одномолекулярную гидовую РНК, в которой часть crRNA связана с частью tracrRNA.
30. Способ по п. 29, предусматривающий, что гидовая РНК содержит последовательность, представленную под SEQ ID NO: 1420, 256, 257 или 258.
31. Способ по любому из пп. 1-28, предусматривающий, что часть crRNA и часть tracrRNA являются отдельными молекулами РНК.
32. Способ по п. 31, предусматривающий, что часть crRNA содержит последовательность, представленную под SEQ ID NO: 1421, и/или часть tracrRNA содержит последовательность, представленную под SEQ ID NO: 1422.
33. Способ по любому из предыдущих пунктов, предусматривающий, что гидовая РНК содержит модификацию, обеспечивающую измененную или регулируемую стабильность.
34. Способ по любому из предыдущих пунктов, предусматривающий, что клетка находится в условиях ex vivo или in vivo.
35. Способ по любому из предыдущих пунктов, предусматривающий, что клетка представляет собой клетку мыши, клетку крысы или клетку человека.
36. Способ по любому из предыдущих пунктов, предусматривающий, что клетка представляет собой клетку печени человека, клетку печени мыши, плюрипотентную клетку мыши или плюрипотентную клетку крысы.
37. Способ по п. 36, предусматривающий, что клетка представляет собой клетку печени человека.
38. Способ по п. 37, предусматривающий, что клетка находится в условиях in vivo.
39. Способ по п. 38, предусматривающий, что белок Cas или нуклеиновую кислоту, кодирующую белок Cas, и гидовую РНК, или ДНК, кодирующую гидовую РНК, вводят в печень in vivo.
40. Способ по любому из предыдущих пунктов, предусматривающий, что клетка представляет собой клетку человека, и причем:
(a) целевая для гидовой РНК последовательность содержит любую из SEQ ID NO: 226-239; и/или
(b) нацеливающий на ДНК сегмент содержит любую из SEQ ID NO: 1629-1642; и/или
(с) гидовая РНК содержит любую из SEQ ID NO: 706-719; 936-949; 1166-1179 и 1396-1409.
41. Способ по любому из пп. 1-36, предусматривающий, что клетка представляет собой клетку мыши, и причем:
(a) целевая для гидовой РНК последовательность содержит любую из SEQ ID NO: 264-268; и/или
(b) нацеливающий на ДНК сегмент содержит любую из SEQ ID NO: 1648-1652; и/или
(c) гидовая РНК содержит любую из SEQ ID NO: 725-729, 955-959, 1185-1189 и 1415-1419.
RU2021133626A 2017-01-23 2018-01-19 Варианты hsd17b13 и их применения RU2021133626A (ru)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201762449335P 2017-01-23 2017-01-23
US62/449,335 2017-01-23
US201762472972P 2017-03-17 2017-03-17
US62/472,972 2017-03-17
US201762581918P 2017-11-06 2017-11-06
US62/581,918 2017-11-06

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
RU2019126354A Division RU2760851C2 (ru) 2017-01-23 2018-01-19 Варианты hsd17b13 и их применения

Publications (1)

Publication Number Publication Date
RU2021133626A true RU2021133626A (ru) 2022-01-31

Family

ID=61768397

Family Applications (3)

Application Number Title Priority Date Filing Date
RU2019126483A RU2019126483A (ru) 2017-01-23 2018-01-19 Варианты 17-бета-гидроксистероиддегидрогеназы 13 (hsd17b13) и их применение
RU2021133626A RU2021133626A (ru) 2017-01-23 2018-01-19 Варианты hsd17b13 и их применения
RU2019126354A RU2760851C2 (ru) 2017-01-23 2018-01-19 Варианты hsd17b13 и их применения

Family Applications Before (1)

Application Number Title Priority Date Filing Date
RU2019126483A RU2019126483A (ru) 2017-01-23 2018-01-19 Варианты 17-бета-гидроксистероиддегидрогеназы 13 (hsd17b13) и их применение

Family Applications After (1)

Application Number Title Priority Date Filing Date
RU2019126354A RU2760851C2 (ru) 2017-01-23 2018-01-19 Варианты hsd17b13 и их применения

Country Status (13)

Country Link
US (5) US11845963B2 (ru)
EP (2) EP3571321A1 (ru)
JP (5) JP7458785B2 (ru)
KR (3) KR20240001333A (ru)
CN (1) CN110199032A (ru)
AU (4) AU2018210364B2 (ru)
BR (1) BR112019014841A2 (ru)
CA (2) CA3049980A1 (ru)
IL (5) IL301053A (ru)
MX (5) MX2019008755A (ru)
RU (3) RU2019126483A (ru)
SG (2) SG11201905508VA (ru)
WO (2) WO2018136758A1 (ru)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7458785B2 (ja) 2017-01-23 2024-04-01 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒドロキシステロイド１７－βデヒドロゲナーゼ１３（ＨＳＤ１７Ｂ１３）バリアント及びその使用
CN110325649A (zh) 2017-04-11 2019-10-11 雷杰纳荣制药公司 用于筛选羟基类固醇(17-β)脱氢酶(HSD17B)家族成员的调节剂的活性的测定法
JP7434151B2 (ja) 2017-10-11 2024-02-20 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｐｎｐｌａ３ ｉ１４８ｍの変異を発現している患者の肝疾患の治療におけるｈｓｄ１７ｂ１３の阻害
CA3093547A1 (en) * 2018-03-21 2019-09-26 Ionis Pharmaceuticals, Inc. Modulation of hsd17b13 expression
EP3768838A1 (en) 2018-03-21 2021-01-27 Regeneron Pharmaceuticals, Inc. 17ß-HYDROXYSTEROID DEHYDROGENASE TYPE 13 (HSD17B13) IRNA COMPOSITIONS AND METHODS OF USE THEREOF
JP2021521788A (ja) 2018-04-19 2021-08-30 ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア ゲノム編集のための組成物および方法
EP3852769A4 (en) * 2018-09-19 2023-12-13 Arrowhead Pharmaceuticals, Inc. ARNI AGENTS FOR INHIBITING EXPRESSION OF 17BETA-HSD TYPE 13- (HSD17B13), THEIR COMPOSITIONS AND METHODS OF USE
AU2019403447B2 (en) * 2018-12-21 2023-07-27 Ionis Pharmaceuticals, Inc. Modulators of HSD17B13 expression
WO2021003295A1 (en) 2019-07-02 2021-01-07 Regeneron Pharmaceuticals, Inc. Modulators of hsd17b13 and methods of use thereof
CN112626199A (zh) * 2021-01-04 2021-04-09 杭州艾迪康医学检验中心有限公司 检测慢性肝炎转化为肝硬化的风险预测位点的引物和方法
CA3216332A1 (en) * 2021-04-22 2022-10-27 Tuojie Biotech (Shanghai) Co., Ltd. Sirna targeting 17b-hydroxysteroid dehydrogenase type 13 and sirna conjugate
WO2023091644A2 (en) * 2021-11-19 2023-05-25 Wave Life Sciences Ltd. Hsd17b13-related double stranded oligonucleotide compositions and methods relating thereto

Family Cites Families (315)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4209A (en) * 1845-09-27 Straw-cutter
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US5179017A (en) 1980-02-25 1993-01-12 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4634665A (en) 1980-02-25 1987-01-06 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4510245A (en) 1982-11-18 1985-04-09 Chiron Corporation Adenovirus promoter system
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5168062A (en) 1985-01-30 1992-12-01 University Of Iowa Research Foundation Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4751180A (en) 1985-03-28 1988-06-14 Chiron Corporation Expression using fused genes providing for protein product
US4683202A (en) * 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US4935233A (en) 1985-12-02 1990-06-19 G. D. Searle And Company Covalently linked polypeptide cell modulators
US4968615A (en) 1985-12-18 1990-11-06 Ciba-Geigy Corporation Deoxyribonucleic acid segment from a virus
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
JP2828642B2 (ja) 1987-06-24 1998-11-25 ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン ヌクレオシド誘導体
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
JPH03503894A (ja) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション オリゴヌクレオチド　ｎ‐アルキルホスホラミデート
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5294533A (en) 1988-07-05 1994-03-15 Baylor College Of Medicine Antisense oligonucleotide antibiotics complementary to the macromolecular synthesis operon, methods of treating bacterial infections and methods for identification of bacteria
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
EP0497875B1 (en) 1989-10-24 2000-03-22 Isis Pharmaceuticals, Inc. 2' modified oligonucleotides
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
WO1991013080A1 (en) 1990-02-20 1991-09-05 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
DK0455905T3 (da) 1990-05-11 1998-12-07 Microprobe Corp Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider
US5135917A (en) 1990-07-12 1992-08-04 Nova Pharmaceutical Corporation Interleukin receptor expression inhibiting antisense oligonucleotides
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5614617A (en) 1990-07-27 1997-03-25 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
MY107332A (en) 1990-08-03 1995-11-30 Sterling Drug Inc Compounds and methods for inhibiting gene expression.
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
US5596086A (en) 1990-09-20 1997-01-21 Gilead Sciences, Inc. Modified internucleoside linkages having one nitrogen and two carbon atoms
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US5271941A (en) 1990-11-02 1993-12-21 Cho Chung Yoon S Antisense oligonucleotides of human regulatory subunit RI.sub.α of cAMP-dependent protein kinases
EP0556301B1 (en) 1990-11-08 2001-01-10 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
US5786138A (en) 1993-01-29 1998-07-28 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Hyperstabilizing antisense nucleic acid binding agents
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
AU6449394A (en) 1993-03-30 1994-10-24 Sterling Winthrop Inc. Acyclic nucleoside analogs and oligonucleotide sequences containing them
JPH08508491A (ja) 1993-03-31 1996-09-10 スターリング ウインスロップ インコーポレイティド ホスホジエステル結合をアミド結合に置き換えたオリゴヌクレオチド
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
AU693097B2 (en) 1993-06-04 1998-06-25 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Method for treating kaposi's sarcoma with antisense oligonucleotides
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5578716A (en) 1993-12-01 1996-11-26 Mcgill University DNA methyltransferase antisense oligonucleotides
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5641754A (en) 1994-01-10 1997-06-24 The Board Of Regents Of The University Of Nebraska Antisense oligonucleotide compositions for selectively killing cancer cells
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5624813A (en) 1994-04-21 1997-04-29 Mahant; Vijay K. NAD(P)+ /NAD(P)H based chemiluminescent diagnostics
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
WO1996005298A1 (en) 1994-08-09 1996-02-22 Ciba-Geigy Ag Antitumor antisense oligonucleotides
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5856103A (en) 1994-10-07 1999-01-05 Board Of Regents The University Of Texas Method for selectively ranking sequences for antisense targeting
US5994320A (en) 1995-02-06 1999-11-30 Regents Of The University Of Minnesota Antisense oligonucleotides and methods for treating central nervous system tumors
IT1275862B1 (it) 1995-03-03 1997-10-24 Consiglio Nazionale Ricerche Trascritto antisenso associato ad alcuni tipi di cellule tumorali ed oligodeossinucleotidi sintetici utili nella diagnosi e nel trattamento
US6040296A (en) 1995-06-07 2000-03-21 East Carolina University Specific antisense oligonucleotide composition & method for treatment of disorders associated with bronchoconstriction and lung inflammation
FR2739029B1 (fr) 1995-09-21 1997-11-21 Roussel Uclaf Nouvelle application therapeutique des composes antimineralo-corticoides
WO1997014709A1 (en) 1995-10-13 1997-04-24 F. Hoffmann-La Roche Ag Antisense oligomers
AU708096B2 (en) 1995-11-21 1999-07-29 Icn Pharmaceuticals, Inc. Inhibition of tumor growth by antisense oligonucleotides for IL-8 and IL-8 receptor
AU1067697A (en) 1995-12-05 1997-06-27 Jouko Antero Oikarinen Hsd17b1 promoter, enhancer, silencer and use thereof
CA2246503A1 (en) 1996-02-15 1997-08-21 National Institutes Of Health Rnase l activators and antisense oligonucleotides effective to treat rsv infections
US5955590A (en) 1996-07-15 1999-09-21 Worcester Foundation For Biomedical Research Conjugates of minor groove DNA binders with antisense oligonucleotides
US6046004A (en) 1997-02-27 2000-04-04 Lorne Park Research, Inc. Solution hybridization of nucleic acids with antisense probes having modified backbones
JPH1142091A (ja) 1997-07-25 1999-02-16 Toagosei Co Ltd アンチセンス核酸化合物
US6391311B1 (en) * 1998-03-17 2002-05-21 Genentech, Inc. Polypeptides having homology to vascular endothelial cell growth factor and bone morphogenetic protein 1
CA2248762A1 (en) 1997-10-22 1999-04-22 University Technologies International, Inc. Antisense oligodeoxynucleotides regulating expression of tnf-.alpha.
PT1490386E (pt) 1998-03-10 2008-11-24 Genentech Inc Novos polipéptidos e ácidos nucleicos que os codificam
TR200002784T2 (tr) 1998-03-11 2000-12-21 Endorecherche, Inc Tip 5 ve tip 3 17beta-Hidroksisteroid dehidrojenaz inhibitörleri ve bunların kullanımı için metodlar
US6007995A (en) 1998-06-26 1999-12-28 Isis Pharmaceuticals Inc. Antisense inhibition of TNFR1 expression
US6599692B1 (en) 1999-09-14 2003-07-29 Sangamo Bioscience, Inc. Functional genomics using zinc finger proteins
US6013522A (en) 1999-02-23 2000-01-11 Isis Pharmaceuticals Inc. Antisense inhibition of human Smad1 expression
US20030104526A1 (en) 1999-03-24 2003-06-05 Qiang Liu Position dependent recognition of GNN nucleotide triplets by zinc fingers
US6025198A (en) 1999-06-25 2000-02-15 Isis Pharmaceuticals Inc. Antisense modulation of Ship-2 expression
US6033910A (en) 1999-07-19 2000-03-07 Isis Pharmaceuticals Inc. Antisense inhibition of MAP kinase kinase 6 expression
FR2801218B1 (fr) 1999-11-23 2001-12-28 Hoechst Marion Roussel Inc Compositions pharmaceutiques comprenant de la trimegestone, leurs procedes de preparation ainsi que le conditionnement primaire les renfermant
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AU2884102A (en) 2000-12-07 2002-06-18 Sangamo Biosciences Inc Regulation of angiogenesis with zinc finger proteins
US7273923B2 (en) 2001-01-22 2007-09-25 Sangamo Biosciences, Inc. Zinc finger proteins for DNA binding and gene regulation in plants
US7947469B2 (en) 2001-01-22 2011-05-24 Gendaq, Ltd. Modulation of HIV infection
US8106255B2 (en) 2002-01-23 2012-01-31 Dana Carroll Targeted chromosomal mutagenasis using zinc finger nucleases
EP2368982A3 (en) 2002-03-21 2011-10-12 Sangamo BioSciences, Inc. Methods and compositions for using zinc finger endonucleases to enhance homologous recombination
CA2497913C (en) 2002-09-05 2014-06-03 California Institute Of Technology Use of chimeric nucleases to stimulate gene targeting
US7754709B2 (en) 2003-06-10 2010-07-13 Solvay Pharmaceuticals Bv Tetracyclic thiophenepyrimidinone compounds as inhibitors of 17β hydroxysteroid dehydrogenase compounds
US7888121B2 (en) 2003-08-08 2011-02-15 Sangamo Biosciences, Inc. Methods and compositions for targeted cleavage and recombination
US8409861B2 (en) 2003-08-08 2013-04-02 Sangamo Biosciences, Inc. Targeted deletion of cellular DNA sequences
US20090169585A1 (en) 2003-10-23 2009-07-02 Resveratrol Partners, Llc Resveratrol-Containing Compositions And Their Use In Modulating Gene Product Concentration Or Activity
US20050158376A1 (en) 2003-10-23 2005-07-21 Sardi William F. Dietary supplement and method of processing same
WO2005108415A2 (en) * 2004-04-30 2005-11-17 Biogen Idec Ma Inc. Membrane associated molecules
EP1745154B1 (en) 2004-05-07 2012-08-01 Celera Corporation Genetic polymorphisms associated with liver fibrosis methods of detection and uses thereof
KR20070060115A (ko) 2004-09-16 2007-06-12 상가모 바이오사이언스 인코포레이티드 단백질 생산을 위한 조성물 및 방법
FR2904000A1 (fr) 2006-07-19 2008-01-25 Galderma Res & Dev S N C Snc Modulateurs de hsd17b7 dans le traitement de l'acne ou de l'hyperseborrhee
US20090203602A1 (en) 2006-09-01 2009-08-13 Cohava Gelber Compositions and methods for diagnosis and treatment of type 2 diabetes
US20080300170A1 (en) 2006-09-01 2008-12-04 Cohava Gelber Compositions and methods for diagnosis and treatment for type 2 diabetes
US20100267052A1 (en) 2006-09-01 2010-10-21 American Type Culture Collection Compositions and methods for diagnosis and treatment of type 2 diabetes
US7951776B2 (en) 2006-09-01 2011-05-31 American Type Culture Collection Methods for treatment of type 1 diabetes
WO2008091873A2 (en) 2007-01-24 2008-07-31 Dana-Farber Cancer Institute, Inc. Compositions and methods for the identification, assessment, prevention and therapy of thymic lymphoma or hamartomatous tumours
AU2007334468B2 (en) 2006-12-14 2013-02-07 Corteva Agriscience Llc Optimized non-canonical zinc finger proteins
WO2009039195A1 (en) 2007-09-20 2009-03-26 Resveratrol Partners, Llc Resveratrol-containing compositions for modulating gene product concentration or activity
CN102037594A (zh) 2008-04-11 2011-04-27 Utc电力公司 燃料电池和具有歧管贮槽的双极板
WO2009148137A1 (ja) 2008-06-04 2009-12-10 協和発酵キリン株式会社 肥満細胞の脱顆粒を制御する核酸
WO2010028110A2 (en) * 2008-09-04 2010-03-11 Board Of Regents, The University Of Texas System Sequence variations in pnpla3 associated with hepatic steatosis
US20100209427A1 (en) 2008-09-24 2010-08-19 Yu Li Lysine acetylation sites
EP2177615A1 (en) 2008-10-10 2010-04-21 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for a genome wide identification of expression regulatory sequences and use of genes and molecules derived thereof for the diagnosis and therapy of metabolic and/or tumorous diseases
WO2010064702A1 (ja) 2008-12-05 2010-06-10 国立大学法人 東京大学 癌の予後を予測するためのバイオマーカー
US20110239315A1 (en) 2009-01-12 2011-09-29 Ulla Bonas Modular dna-binding domains and methods of use
EP2206723A1 (en) 2009-01-12 2010-07-14 Bonas, Ulla Modular DNA-binding domains
CA2697169A1 (en) 2009-03-18 2010-09-18 David Stojdl Compositions and methods for augmenting activity of oncolytic viruses
US8871905B2 (en) 2009-03-20 2014-10-28 Sangamo Biosciences, Inc. Modification of CXCR4 using engineered zinc finger proteins
US20120028816A1 (en) 2009-03-31 2012-02-02 Warren Stephen T Methods and systems for screening for and diagnosing dna methylation associated with autism spectrum disorders
US8772008B2 (en) 2009-05-18 2014-07-08 Sangamo Biosciences, Inc. Methods and compositions for increasing nuclease activity
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
DK3329772T3 (da) 2009-07-15 2020-01-27 Calimmune Inc Dobbeltvektor til inhibering af human immundefektvirus
WO2011006214A1 (en) 2009-07-16 2011-01-20 Peter Maccallum Cancer Institute Method of detecting radiation exposure and adverse toxicity thereto
US20120178647A1 (en) 2009-08-03 2012-07-12 The General Hospital Corporation Engineering of zinc finger arrays by context-dependent assembly
WO2011020014A1 (en) 2009-08-14 2011-02-17 Regeneron Pharmaceuticals, Inc. Promoter-regulated differentiation-dependent self-deleting cassette
CN106191126B (zh) 2009-10-29 2020-04-14 瑞泽恩制药公司 多功能等位基因
WO2011066458A2 (en) 2009-11-25 2011-06-03 Prometheus Laboratories Inc. Novel genomic biomarkers for irritable bowel syndrome diagnosis
BR112012014080A2 (pt) 2009-12-10 2015-10-27 Univ Iowa State Res Found método para modificação do material genético, método para geração de um ácido nucleico, monômero de endonuclease efetora tal, método para geração de um aninal, método para geração de uma planta, método para recombinação genética direcionada, ácido nucleico, cassete de expressão e célula hospedeira
WO2011084747A2 (en) 2009-12-21 2011-07-14 The Johns Hopkins University Compositions and methods for somatic tissue induced pluripotent stem cells having an endoderm origin
US20130029873A1 (en) 2010-04-12 2013-01-31 University Health Network Methods and compositions for diagnosing pulmonary fibrosis subtypes and assessing the risk of primary graft dysfunction after lung transplantation
WO2011128096A1 (en) 2010-04-16 2011-10-20 Roche Diagnostics Gmbh Polymorphism markers for predicting response to interleukin-6 receptor-inhibiting monoclonal antibody drug treatment
EP2569446B1 (en) 2010-05-12 2018-07-11 Steven E. Schutzer Diagnostic markers for neuropsychiatric diseasen
WO2011145121A1 (en) 2010-05-18 2011-11-24 Scatolificio Mogliani S.N.C. Di Mogliani Mauro E Andrea Cardboard box for stable stacking with other identical specimens
US8945847B2 (en) 2010-05-24 2015-02-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Methods and kits for ascertaining biosafety of an agent
US20120058088A1 (en) 2010-06-28 2012-03-08 Resveratrol Partners, Llc Resveratrol-Containing Compositions And Methods Of Use
CN103097552B (zh) 2010-07-14 2015-10-07 加利福尼亚大学董事会 用于诊断短暂性缺血发作的生物标志物
US20140045915A1 (en) 2010-08-31 2014-02-13 The General Hospital Corporation Cancer-related biological materials in microvesicles
WO2012052953A1 (en) 2010-10-20 2012-04-26 Fondazione Centro San Raffaele Del Monte Tabor MiRNA
RU2603731C2 (ru) 2010-10-26 2016-11-27 Бак Инститьют Фор Эйдж Рисёрч Понижающая регуляция трансктипции sine/alu ретротранспозонов для индукции или восстановления способности к пролиферации и/или плюрипотентности стволовой клетки
DK2638163T3 (en) 2010-11-12 2017-07-24 Massachusetts Gen Hospital POLYCOMB-ASSOCIATED NON-CODING RNAs
US9920317B2 (en) 2010-11-12 2018-03-20 The General Hospital Corporation Polycomb-associated non-coding RNAs
WO2012070014A2 (en) 2010-11-26 2012-05-31 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Identification of novel cell surface markers for pancreatic progenitor cells and definite endodermal cells
WO2012080816A2 (en) 2010-12-16 2012-06-21 Norwegian University Of Science And Technology (Ntnu) Single nucleotide polymorphism associated with risk of insulin resistance development
DK2655621T3 (en) 2010-12-20 2018-08-13 Massachusetts Gen Hospital Polycomb-associated non-coding RNAS
WO2012151346A1 (en) 2011-05-03 2012-11-08 Dermachip Inc. Expression signatures of genes and gene networks associated with skin aging
GB201112246D0 (en) 2011-07-15 2011-08-31 Univ Birmingham Diagnosis of alzheimer's disease
US20130079241A1 (en) 2011-09-15 2013-03-28 Jianhua Luo Methods for Diagnosing Prostate Cancer and Predicting Prostate Cancer Relapse
WO2013126565A1 (en) 2012-02-24 2013-08-29 Lunyak Victoria V Downregulation of sine/alu retrotransposon transcription to induce or restore proliferative capacity and/or pluripotency to a stem cell
WO2013141680A1 (en) 2012-03-20 2013-09-26 Vilnius University RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX
US9637739B2 (en) 2012-03-20 2017-05-02 Vilnius University RNA-directed DNA cleavage by the Cas9-crRNA complex
WO2013166264A2 (en) 2012-05-02 2013-11-07 University Of Georgia Research Foundation, Inc. Methods for altering virus replication
WO2013177060A2 (en) 2012-05-20 2013-11-28 Trustees Of Boston University Methods and systems for monitoring, diagnosing, and treating chronic obstructive polmonary disease
PE20190844A1 (es) * 2012-05-25 2019-06-17 Emmanuelle Charpentier Modulacion de transcripcion con arn de direccion a adn generico
WO2013190075A2 (en) 2012-06-20 2013-12-27 Meyer Helmut E Specific biomarkers for hepatocellular carcinoma (hcc)
US20140004153A1 (en) 2012-07-02 2014-01-02 Lancell, L.L.C. Use of somatic mutations in the extracellular domain of transmembrane proteins in a patient's tumor as immunogens for active humoral immunotherapy of cancer
WO2014028946A2 (en) 2012-08-17 2014-02-20 The Broad Institute, Inc. Modulators of hepatic lipoprotein metabolism
WO2014033644A2 (en) 2012-08-28 2014-03-06 Novartis Ag Methods of nuclease-based genetic engineering
US9375433B2 (en) 2012-09-26 2016-06-28 Tangent Reprofiling Limited Modulators of androgen synthesis
EP2900270B1 (en) 2012-09-26 2019-03-06 Tangent Reprofiling Limited Combination of benzo(iso)oxazolepiperidines with conjugated linoleic acid
KR101706085B1 (ko) 2012-10-23 2017-02-14 주식회사 툴젠 표적 DNA에 특이적인 가이드 RNA 및 Cas 단백질을 암호화하는 핵산 또는 Cas 단백질을 포함하는, 표적 DNA를 절단하기 위한 조성물 및 이의 용도
ES2657608T3 (es) 2012-12-05 2018-03-06 Alnylam Pharmaceuticals, Inc. Composiciones de arni de pcsk9 y métodos de uso de las mismas
KR102145760B1 (ko) 2012-12-06 2020-08-19 시그마-알드리치 컴퍼니., 엘엘씨 Crispr-기초된 유전체 변형과 조절
EP2929035A1 (en) 2012-12-07 2015-10-14 Shire Human Genetic Therapies, Inc. Lipidic nanoparticles for mrna delivering
EP3045537A1 (en) 2012-12-12 2016-07-20 The Broad Institute, Inc. Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains
EP4299741A3 (en) 2012-12-12 2024-02-28 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
KR20150095861A (ko) 2012-12-17 2015-08-21 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 Rna-가이드된 인간 게놈 조작
CA2900992C (en) 2013-02-20 2023-02-28 Regeneron Pharmaceuticals, Inc. Genetic modification of rats
JP2016507244A (ja) 2013-02-27 2016-03-10 ヘルムホルツ・ツェントルム・ミュンヒェン・ドイチェス・フォルシュンクスツェントルム・フューア・ゲズントハイト・ウント・ウムベルト（ゲーエムベーハー）Ｈｅｌｍｈｏｌｔｚ Ｚｅｎｔｒｕｍ ＭｕｅｎｃｈｅｎＤｅｕｔｓｃｈｅｓ Ｆｏｒｓｃｈｕｎｇｓｚｅｎｔｒｕｍ ｆｕｅｒ Ｇｅｓｕｎｄｈｅｉｔ ｕｎｄ Ｕｍｗｅｌｔ （ＧｍｂＨ） Ｃａｓ９ヌクレアーゼによる卵母細胞における遺伝子編集
US20160032395A1 (en) 2013-03-14 2016-02-04 Elai Davicioni Cancer biomarkers and classifiers and uses thereof
US20160184458A1 (en) 2013-03-14 2016-06-30 Shire Human Genetic Therapies, Inc. Mrna therapeutic compositions and use to treat diseases and disorders
EP2968988A4 (en) * 2013-03-14 2016-11-16 Allegro Diagnostics Corp METHOD FOR EVALUATING A COPD STATUS
EP2971128B1 (en) 2013-03-15 2023-03-01 Veracyte, Inc. Biomarkers for diagnosis of lung diseases and methods of use thereof
EP3741868A1 (en) 2013-03-15 2020-11-25 The General Hospital Corporation Rna-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci
US20140329704A1 (en) 2013-03-28 2014-11-06 President And Fellows Of Harvard College Markers for mature beta-cells and methods of using the same
JP2016522679A (ja) 2013-04-04 2016-08-04 プレジデント アンド フェローズ オブ ハーバード カレッジ ＣＲＩＳＰＲ／Ｃａｓ系を用いたゲノム編集の治療的使用
GB201306536D0 (en) 2013-04-10 2013-05-22 Gt Biolog Ltd Polypeptide and immune modulation
US10604771B2 (en) 2013-05-10 2020-03-31 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
EP3004376B1 (en) 2013-06-03 2018-05-09 Nestec S.A. Methods for diagnosing chronic valvular disease
WO2014197453A1 (en) 2013-06-03 2014-12-11 The Trustees Of Columbia University In The City Of New York Recurrent mutations in epigenetic regulators, rhoa and fyn kinase in peripheral t-cell lymphomas
US9267135B2 (en) 2013-06-04 2016-02-23 President And Fellows Of Harvard College RNA-guided transcriptional regulation
BR112015031611A2 (pt) 2013-06-17 2017-12-12 Massachusetts Inst Technology aplicação, manipulação e otimização de sistemas, métodos e composições para direcionamento e modelação de doenças e distúrbios de células pós-mitóticas
EP3011031B1 (en) 2013-06-17 2020-09-30 The Broad Institute Inc. Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy
WO2015008166A2 (en) 2013-07-12 2015-01-22 Casey Patrick J Method for the harvesting, processing, and storage of proteins from the mammalian feto-placental unit and use of such proteins in compositions and medical treatment
US20150079062A1 (en) 2013-07-12 2015-03-19 Patrick J. Casey Method for harvesting, processing, and storage of proteins from the mammalian feto-placental unit and use of such proteins in compositions and medical treatment
RU2545990C2 (ru) 2013-07-16 2015-04-10 Государственное бюджетное учреждение здравоохранения города Москвы Московский клинический научно-практический центр Департамента здравоохранения города Москвы Способ дифференциальной диагностики стеатоза печени и стеатогепатита
EP3058072B1 (en) 2013-10-17 2021-05-19 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
EA201690576A1 (ru) 2013-10-22 2016-10-31 Шир Хьюман Дженетик Терапис, Инк. Липидные композиции для доставки матричной рнк
CN103520724B (zh) 2013-10-23 2016-05-25 江苏美迪森生物医药有限公司 Hsd17b13蛋白或其编码基因的抑制剂的新用途
GB201320061D0 (en) 2013-11-13 2013-12-25 Electrophoretics Ltd Materials nad methods for diagnosis and prognosis of liver cancer
WO2015127439A1 (en) 2014-02-24 2015-08-27 Sangamo Biosciences, Inc. Methods and compositions for nuclease-mediated targeted integration
CN106456644B (zh) 2014-05-09 2021-06-15 坦吉特雷普罗菲林有限公司 雄激素合成调节剂
EP3155116A4 (en) 2014-06-10 2017-12-27 Massachusetts Institute Of Technology Method for gene editing
BR112016029178A2 (pt) 2014-06-16 2017-10-17 Univ Johns Hopkins composições e métodos para a expressão de rnas guia de crispr usando o promotor h1
US10588980B2 (en) 2014-06-23 2020-03-17 Novartis Ag Fatty acids and their use in conjugation to biomolecules
US20150376587A1 (en) 2014-06-25 2015-12-31 Caribou Biosciences, Inc. RNA Modification to Engineer Cas9 Activity
WO2016004387A1 (en) 2014-07-02 2016-01-07 H. Lee Moffitt Cancer Center And Research Institute, Inc. Gene expression signature for cancer prognosis
CA2955157A1 (en) 2014-07-14 2016-01-21 Patrick J. Casey Method for the harvesting, processing, and storage of proteins from the mammalian feto-placental unit and use of such proteins in compositions and medical treatment
US20170247758A1 (en) 2014-08-18 2017-08-31 Drexel University Methods, computer-readable media, and systems for assessing samples and wounds, predicting whether a wound will heal, and monitoring effectiveness of a treatment
CN114606309A (zh) 2014-11-05 2022-06-10 威拉赛特公司 使用机器学习和高维转录数据的诊断系统和方法
EP3256587A2 (en) 2015-02-13 2017-12-20 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
CN104698108B (zh) 2015-03-26 2016-11-09 中国药科大学 一种利用固定化酶筛选I型17β羟类固醇脱氢酶抑制剂的方法
EP3350328A1 (en) 2015-09-14 2018-07-25 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof
EP3159407A1 (en) 2015-10-23 2017-04-26 Silence Therapeutics (London) Ltd Guide rnas, methods and uses
JP2018536689A (ja) 2015-12-10 2018-12-13 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． ステロール調節エレメント結合タンパク質（ＳＲＥＢＰ）シャペロン（ＳＣＡＰ）ｉＲＮＡ組成物およびその使用方法
CA3005131A1 (en) 2015-12-14 2017-06-22 Cold Spring Harbor Laboratory Antisense oligomers for treatment of tuberous sclerosis complex
CA3005128A1 (en) 2015-12-14 2017-06-22 Cold Spring Harbor Laboratory Compositions and methods for treatment of eye diseases
WO2017106364A2 (en) 2015-12-14 2017-06-22 Cold Spring Harbor Laboratory Compositions and methods for treatment of retinitis pigmentosa 18 and retinitis pigmentosa 13
EP3390666A4 (en) 2015-12-14 2019-08-07 Cold Spring Harbor Laboratory COMPOSITIONS AND METHODS FOR TREATING RENAL DISEASES
EP3389725B1 (en) 2015-12-14 2022-04-06 Cold Spring Harbor Laboratory Compositions and methods for treatment of central nervous system diseases
EP3389671A4 (en) 2015-12-14 2019-07-17 Cold Spring Harbor Laboratory ANTISENSE OLIGOMERS FOR THE TREATMENT OF ALAGILLE'S SYNDROME
JP2019500345A (ja) 2015-12-14 2019-01-10 コールド スプリング ハーバー ラボラトリー 肝臓病の処置のための組成物および方法
US20190071795A1 (en) 2016-03-09 2019-03-07 Molecular Stethoscope, Inc. Methods and systems for detecting tissue conditions
CA3221950A1 (en) 2016-03-16 2017-09-21 Spogen Biotech Inc. Methods for promoting plant health using free enzymes and microorganisms that overexpress enzymes
EP3452101A2 (en) 2016-05-04 2019-03-13 CureVac AG Rna encoding a therapeutic protein
US10036024B2 (en) 2016-06-03 2018-07-31 Purdue Research Foundation siRNA compositions that specifically downregulate expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD)
GB201609977D0 (en) 2016-06-08 2016-07-20 Cancer Rec Tech Ltd Chemosensitivity predictive biomarkers
US10767175B2 (en) 2016-06-08 2020-09-08 Agilent Technologies, Inc. High specificity genome editing using chemically modified guide RNAs
WO2018107028A1 (en) 2016-12-08 2018-06-14 Intellia Therapeutics, Inc. Modified guide rnas
EP3551169A4 (en) 2016-12-09 2020-09-09 Sangamo Therapeutics, Inc. ADMINISTRATION OF TARGET-SPECIFIC NUCLEASES
KR20240027888A (ko) 2016-12-14 2024-03-04 리간달 인코포레이티드 핵산 및 단백질 페이로드 전달을 위한 방법 및 조성물
JP7458785B2 (ja) 2017-01-23 2024-04-01 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒドロキシステロイド１７－βデヒドロゲナーゼ１３（ＨＳＤ１７Ｂ１３）バリアント及びその使用
CN111108207A (zh) 2017-06-02 2020-05-05 国家健康与医学研究院 用于遗传障碍的基因疗法的基因组编辑手段和结合病毒载体的基因疗法
JP7434151B2 (ja) 2017-10-11 2024-02-20 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｐｎｐｌａ３ ｉ１４８ｍの変異を発現している患者の肝疾患の治療におけるｈｓｄ１７ｂ１３の阻害
CA3093547A1 (en) 2018-03-21 2019-09-26 Ionis Pharmaceuticals, Inc. Modulation of hsd17b13 expression
EP3768838A1 (en) 2018-03-21 2021-01-27 Regeneron Pharmaceuticals, Inc. 17ß-HYDROXYSTEROID DEHYDROGENASE TYPE 13 (HSD17B13) IRNA COMPOSITIONS AND METHODS OF USE THEREOF
US11690921B2 (en) 2018-05-18 2023-07-04 Sangamo Therapeutics, Inc. Delivery of target specific nucleases
KR20210029772A (ko) 2018-06-08 2021-03-16 인텔리아 테라퓨틱스, 인크. 유전자 편집을 위한 변형된 가이드 rna
WO2019246203A1 (en) 2018-06-19 2019-12-26 The Board Of Regents Of The University Of Texas System Lipid nanoparticle compositions for delivery of mrna and long nucleic acids

Also Published As

Publication number Publication date
IL293377B2 (en) 2023-08-01
JP7458785B2 (ja) 2024-04-01
CA3047429A1 (en) 2018-07-26
IL285053B (en) 2022-07-01
EP3571321A1 (en) 2019-11-27
US20180216084A1 (en) 2018-08-02
IL267925A (en) 2019-09-26
JP2024038085A (ja) 2024-03-19
AU2022203239A1 (en) 2022-06-02
JP2023175705A (ja) 2023-12-12
JP7425106B2 (ja) 2024-01-30
CA3049980A1 (en) 2018-07-26
JP2020505920A (ja) 2020-02-27
KR20240001333A (ko) 2024-01-03
AU2018209950B2 (en) 2023-02-09
AU2018209950A1 (en) 2019-09-12
SG11201906735RA (en) 2019-08-27
MX2022015079A (es) 2023-01-18
AU2018210364A1 (en) 2019-08-15
US11753628B2 (en) 2023-09-12
US20180216104A1 (en) 2018-08-02
US11845963B2 (en) 2023-12-19
CN110446785A (zh) 2019-11-12
RU2019126354A (ru) 2021-02-24
US10787647B2 (en) 2020-09-29
AU2018210364B2 (en) 2022-03-17
NZ755715A (en) 2021-10-29
IL301053A (en) 2023-05-01
RU2019126483A (ru) 2021-02-24
RU2019126483A3 (ru) 2021-06-29
SG11201905508VA (en) 2019-08-27
KR102619197B1 (ko) 2024-01-03
IL293377B1 (en) 2023-04-01
IL293377A (en) 2022-07-01
IL268156A (en) 2019-09-26
KR20190111067A (ko) 2019-10-01
US20200354693A1 (en) 2020-11-12
MX2019008675A (es) 2019-09-18
KR20190112004A (ko) 2019-10-02
US11485958B2 (en) 2022-11-01
US20220267743A1 (en) 2022-08-25
IL267925B (en) 2021-08-31
CN110199032A (zh) 2019-09-03
RU2019126354A3 (ru) 2021-05-04
RU2760851C2 (ru) 2021-11-30
MX2019008755A (es) 2019-12-16
MX2022015081A (es) 2023-01-18
WO2018136758A1 (en) 2018-07-26
JP2020513784A (ja) 2020-05-21
JP2022095909A (ja) 2022-06-28
JP7094963B2 (ja) 2022-07-04
WO2018136702A1 (en) 2018-07-26
US20230031669A1 (en) 2023-02-02
BR112019014841A2 (pt) 2020-04-28
AU2023202663A1 (en) 2023-05-25
EP3571301A1 (en) 2019-11-27
IL285053A (en) 2021-08-31
MX2022015080A (es) 2023-01-18

Similar Documents

Publication Publication Date Title
RU2021133626A (ru) Варианты hsd17b13 и их применения
US20230340456A1 (en) Use of exonucleases to improve crispr/cas-mediated genome editing
US11479767B2 (en) Modified guide RNAs
Mangeot et al. Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins
US20230233651A1 (en) Materials and methods for treatment of titin-based myopathies and other titinopathies
Lao et al. HPV oncogene manipulation using nonvirally delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute
US20220307020A1 (en) Methods and compositions for editing rnas
CN109715801B (zh) 用于治疗α1抗胰蛋白酶缺乏的材料和方法
TW202028466A (zh) 編輯RNAs的方法以及組成物
JP2023546597A (ja) 部位特異的標的化エレメントによるプログラム可能な付加（ｐａｓｔｅ）を使用した部位特異的遺伝子操作のためのシステム、方法及び組成物
TW202028461A (zh) 核酸構築體及使用方法
CN111684070A (zh) 用于a型血友病基因编辑的组合物和方法
CN111269902A (zh) Crispr-cas系统和组合物的递送及用途
JP2020513784A5 (ru)
WO2018117746A1 (ko) 동물 배아의 염기 교정용 조성물 및 염기 교정 방법
Li et al. Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research
US20210254057A1 (en) Compositions and methods for gene editing by targeting transferrin
Ryan et al. Phosphonoacetate modifications enhance the stability and editing yields of guide RNAs for Cas9 editors
EP4230737A1 (en) Novel enhanced base editing or revising fusion protein and use thereof
JP2022554162A (ja) 修飾二重鎖ドナー鋳型
Suzuki Targeted gene modification by oligonucleotides and small DNA fragments in eukaryotes
JP7472121B2 (ja) アルブミン遺伝子座からの導入遺伝子発現のための組成物及び方法
US20230365992A1 (en) Novel enhanced base editing or revising fusion protein and use thereof
CN111004816A (zh) 基于Cas12a技术的外源基因定点敲入方法