RU2021120582A - Мутации фермента crispr, уменьшающие нецелевые эффекты - Google Patents
Мутации фермента crispr, уменьшающие нецелевые эффекты Download PDFInfo
- Publication number
- RU2021120582A RU2021120582A RU2021120582A RU2021120582A RU2021120582A RU 2021120582 A RU2021120582 A RU 2021120582A RU 2021120582 A RU2021120582 A RU 2021120582A RU 2021120582 A RU2021120582 A RU 2021120582A RU 2021120582 A RU2021120582 A RU 2021120582A
- Authority
- RU
- Russia
- Prior art keywords
- cas9 protein
- engineered cas9
- modification
- engineered
- activity
- Prior art date
Links
- 108091033409 CRISPR Proteins 0.000 title claims 38
- 230000000694 effects Effects 0.000 title claims 13
- 230000035772 mutation Effects 0.000 title claims 2
- 230000004048 modification Effects 0.000 claims 17
- 238000012986 modification Methods 0.000 claims 17
- 238000006467 substitution reaction Methods 0.000 claims 9
- 230000008685 targeting Effects 0.000 claims 8
- 102220485935 ATP-dependent DNA/RNA helicase DHX36_R63A_mutation Human genes 0.000 claims 5
- 108091033319 polynucleotide Proteins 0.000 claims 5
- 102000040430 polynucleotide Human genes 0.000 claims 5
- 239000002157 polynucleotide Substances 0.000 claims 5
- 239000013598 vector Substances 0.000 claims 5
- 230000035897 transcription Effects 0.000 claims 4
- 238000013518 transcription Methods 0.000 claims 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 3
- 101710163270 Nuclease Proteins 0.000 claims 3
- 235000001014 amino acid Nutrition 0.000 claims 3
- 230000027455 binding Effects 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 239000002773 nucleotide Substances 0.000 claims 3
- 125000003729 nucleotide group Chemical group 0.000 claims 3
- 108020004414 DNA Proteins 0.000 claims 2
- 102000053602 DNA Human genes 0.000 claims 2
- 230000007018 DNA scission Effects 0.000 claims 2
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims 2
- 230000007022 RNA scission Effects 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 230000001105 regulatory effect Effects 0.000 claims 2
- 230000037426 transcriptional repression Effects 0.000 claims 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 1
- 241000589941 Azospirillum Species 0.000 claims 1
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 claims 1
- 241000589876 Campylobacter Species 0.000 claims 1
- 241000032681 Gluconacetobacter Species 0.000 claims 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- 108010033040 Histones Proteins 0.000 claims 1
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 claims 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 1
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 claims 1
- 241000588653 Neisseria Species 0.000 claims 1
- 241000135938 Nitratifractor Species 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 241001386753 Parvibaculum Species 0.000 claims 1
- 241000605947 Roseburia Species 0.000 claims 1
- 108020004682 Single-Stranded DNA Proteins 0.000 claims 1
- 241000949716 Sphaerochaeta Species 0.000 claims 1
- 241000191940 Staphylococcus Species 0.000 claims 1
- 241000194017 Streptococcus Species 0.000 claims 1
- 241000193996 Streptococcus pyogenes Species 0.000 claims 1
- 101000910035 Streptococcus pyogenes serotype M1 CRISPR-associated endonuclease Cas9/Csn1 Proteins 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 229940024606 amino acid Drugs 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 210000003527 eukaryotic cell Anatomy 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 1
- 229960000310 isoleucine Drugs 0.000 claims 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 claims 1
- 102220229936 rs1064795830 Human genes 0.000 claims 1
- 102200006539 rs121913529 Human genes 0.000 claims 1
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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/36—Adaptation or attenuation of 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
- C12N15/10—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
- C12N15/111—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
- C12N15/63—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
- C12N15/86—Viral vectors
-
- 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
-
- 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)
-
- G—PHYSICS
- G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
- G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
- G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
- G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- General Physics & Mathematics (AREA)
- Mycology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Algebra (AREA)
- Mathematical Analysis (AREA)
- Mathematical Physics (AREA)
- Pure & Applied Mathematics (AREA)
- Business, Economics & Management (AREA)
- Educational Administration (AREA)
- Educational Technology (AREA)
- Theoretical Computer Science (AREA)
- Cell Biology (AREA)
- Mathematical Optimization (AREA)
- Computational Mathematics (AREA)
- Medical Informatics (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Bakery Products And Manufacturing Methods Therefor (AREA)
Claims (31)
1. Сконструированный белок Cas9, содержащий по меньшей мере одну модификацию по сравнению с белком Cas9 дикого типа, где указанная модификация включает аминокислотную замену в положении 13, 63, 415, 610, 775, 779, 780, 810, 832, 848, 855, 861, 862, 866, 961, 968, 974, 976, 1000, 1003, 1014, 1047, 1060, 1107, 1108, 1109, 1114, 1129, 1240, 1289, 1296, 1297, 1300, 1311 или 1325 согласно нумерации аминокислотных положений в Cas9 из Streptococcus pyogenes (SpCas9).
2. Сконструированный белок Cas9 по п.1, в котором модификация включает замену Lys, His, Arg, Glu, Asp, Ser, Gly или Thr.
3. Сконструированный белок Cas9 по п.1, в котором модификация включает замену на Gly, Ala, Ile, Glu или Asp.
4. Сконструированный белок Cas9 по п.1, в котором модификация включает аминокислотную замену в связывающей бороздке между доменами RuvC и HNH.
5. Сконструированный белок Cas9 по п.1, в котором модификация включает мутацию в домене RuvCI, RuvCIII, RuvCIII или HNH.
6. Сконструированный белок Cas9 по п.1, в котором модификация в положении 63, 415, 775, 779, 780, 810, 832, 848, 855, 861, 862, 866, 961, 968, 974, 976, 1000, 1003, 1014, 1047, 1060, 1107, 1108, 1109, 1114, 1129, 1240, 1289, 1296, 1297, 1300, 1311 или 1325 включает замещение аланина.
7. Сконструированный белок Cas9 по п.1, в котором модификация в положении 13 включает изолейциновую замену, модификация в положении 610 включает глициновую замену, модификация в положении 799 включает лейциновую замену и/или где модификация в положении 1129 включает глутаминовокислотную замену.
8. Сконструированный белок Cas9 по п.1, отличающийся тем, что модификация включает K775A, E779L, Q807A, R780A, K810A, R832A, K848A, K855A, K862A, K961A, K968A, K974A, R976A, H983A, K1000A, K1014A, K1047A, R1060A, K1003A, S1109A, H1240A, K1289A, K1296A, H1297A, K1300A, H1311A или K1325A.
9. Сконструированный белок Cas9 по п.1, в котором модификация включает R783A и A1322T, или R780A и K810A, или R780A и K855A, или R780A и R976A, или K848A и R976A, или K855A и R976A, или R780A и K848A, или K810A и K848A, или K848A и K855A, или K810A и K855A, или H982A и R1060A, или H982A и R1003A, или K1003A и R1060A, или R780A и H982A, или K810A и H982A, или K848A и H982A, или K855A и H982A, или R780A и K1003A, или K810A и R1003A, или K848A и K1003A, или K848A и K1007A, или R780A и R1060A, или K810A и R1060A, или K848A и R1060A, или R780A и R1114A, или K848A и R1114A, или R63A и K855A, или R63A и H982A, или H415A и R780A, или H415A и K848A, или K848A и E1108A, или K810A и K1003A, или R780A и R1060A, или K810A и R1060A, или K848A и R1060A.
10. Сконструированный белок Cas9 по п.1, в котором модификация включает H982A, K1003A, и K1129E, или R780A, K1003A, и R1060A, или K810A, K1003A, и R1060A, или K848A, K1003A, и R1060A, или K855A, K1003A, и R1060A, или H982A, K1003A, и R1060A, или R63A, K848A, и R1060A, или T13I, R63A, и K810A, или G12D, R63A, и R1060A.
11. Сконструированный белок Cas9 по п.1, в котором модификация включает R63A, E610G, K855A и R1060A; или R63A, K855A, R1060A и E610G.
12. Сконструированный белок Cas9 по п.1, где сконструированный белок Cas9 является мутантом белка Cas9 из рода, включающего Streptococcus, Campylobacter, Nitratifractor, Staphylococcus, Parvibaculum, Roseburia, Neisseria, Gluconacetobacter, Azospirillum, Sphaerochaeta, Lactobacillus, Eubacterium или Corynebacter.
13. Сконструированный белок Cas9 по п.1, где сконструированный белок Cas9 содержит один или несколько доменов сигнала ядерной локализации (NLS).
14. Сконструированный белок Cas9 по п.1, где сконструированный белок Cas9 содержит по меньшей мере два или более NLS.
15. Сконструированный белок Cas9 по п.1, где сконструированный белок Cas9 содержит один или несколько гетерологичных функциональных доменов.
16. Сконструированный белок Cas9 по п.15, в котором один или несколько гетерологичных функциональных доменов содержат один или несколько доменов активации транскрипции.
17. Сконструированный белок Cas9 по п.16, в котором домен активации транскрипции содержит VP64.
18. Сконструированный белок Cas9 по п.15, в котором один или несколько гетерологичных функциональных доменов содержат один или несколько доменов репрессии транскрипции.
19. Сконструированный белок Cas9 по п.18, в котором домен репрессии транскрипции включает домен KRAB или домен SD.
20. Сконструированный белок Cas9 по п.15, в котором один или несколько гетерологичных функциональных доменов содержат один или несколько нуклеазных доменов.
21. Сконструированный белок Cas9 по п.20, в котором нуклеазный домен включает Fok1.
22. Сконструированный белок Cas9 по п.15, в котором один или несколько гетерологичных функциональных доменов обладают одной или несколькими из следующих активностей: активность метилазы, активность деметилазы, активность активации транскрипции, активность репрессии транскрипции, активность фактора высвобождения транскрипции, активность модификации гистонов, нуклеазная активность, активность расщепления одноцепочечной РНК, активность расщепления двухцепочечной РНК, активность расщепления одноцепочечной ДНК, активность расщепления двухцепочечной ДНК и активность связывания нуклеиновых кислот.
23. Молекула нуклеиновой кислоты, содержащая нуклеотидную последовательность, кодирующую сконструированный белок Cas9 по п.1, где нуклеотидная последовательность является оптимизированной по кодонам для экспрессии в эукариоте.
24. Композиция, содержащая сконструированный белок Cas9 по п.1 и один или несколько направляющих полинуклеотидов, содержащих направляющую последовательность, парную tracr-последовательность и tracr-последовательность.
25. Система CRISPR-Cas9, содержащая сконструированный белок Cas9 по п.1 в комплексе с направляющим полинуклеотидом, содержащим направляющую последовательность, парную tracr-последовательность и tracr-последовательность.
26. Векторная система, содержащая один или несколько векторов, причем один или несколько векторов содержат:
а) первый регуляторный элемент, функционально связанный с нуклеотидной последовательностью, кодирующей сконструированный белок Cas9 по п.1; а также
b) второй регуляторный элемент, функционально связанный с одной или несколькими нуклеотидными последовательностями, кодирующими одну или несколько молекул нуклеиновых кислот, содержащих направляющий полинуклеотид, содержащий направляющую последовательность, tracr-последовательность и парную tracr-последовательность, где компоненты (a) и (b) расположены на одном или разных векторах.
27. Выделенная эукариотическая клетка, содержащая векторную систему по п. 26.
28. Способ модификации представляющего интерес целевого локуса, включающий доставку в указанный локус сконструированного белка Cas9 по п.1 и одного или нескольких направляющих полинуклеотидов, при этом сконструированный белок Cas9 образует комплекс с одним или несколькими направляющими полинуклеотидами и после связывания комплекса с представляющим интерес целевым локусом белок Cas9 индуцирует модификацию интересующего целевого локуса.
29. Выделенная клетка-хозяин или линия клеток, содержащая сконструированный белок Cas9 по п.1.
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562181453P | 2015-06-18 | 2015-06-18 | |
| US62/181,453 | 2015-06-18 | ||
| US201562207312P | 2015-08-19 | 2015-08-19 | |
| US62/207,312 | 2015-08-19 | ||
| US201562237360P | 2015-10-05 | 2015-10-05 | |
| US62/237,360 | 2015-10-05 | ||
| US201562255256P | 2015-11-13 | 2015-11-13 | |
| US62/255,256 | 2015-11-13 | ||
| US201562269876P | 2015-12-18 | 2015-12-18 | |
| US62/269,876 | 2015-12-18 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018101710A Division RU2752834C2 (ru) | 2015-06-18 | 2016-06-17 | Мутации фермента crispr, уменьшающие нецелевые эффекты |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2021120582A true RU2021120582A (ru) | 2021-09-02 |
Family
ID=56345216
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2021120582A RU2021120582A (ru) | 2015-06-18 | 2016-06-17 | Мутации фермента crispr, уменьшающие нецелевые эффекты |
| RU2018101710A RU2752834C2 (ru) | 2015-06-18 | 2016-06-17 | Мутации фермента crispr, уменьшающие нецелевые эффекты |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018101710A RU2752834C2 (ru) | 2015-06-18 | 2016-06-17 | Мутации фермента crispr, уменьшающие нецелевые эффекты |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US10876100B2 (ru) |
| EP (2) | EP3929287A3 (ru) |
| JP (3) | JP7107683B2 (ru) |
| KR (2) | KR102575342B1 (ru) |
| CN (2) | CN109536474A (ru) |
| AU (2) | AU2016280893B2 (ru) |
| CA (1) | CA2989830A1 (ru) |
| IL (3) | IL284808B (ru) |
| MX (2) | MX2017016289A (ru) |
| RU (2) | RU2021120582A (ru) |
| SG (1) | SG10201912329YA (ru) |
| TW (2) | TW202400626A (ru) |
| WO (1) | WO2016205613A1 (ru) |
| ZA (1) | ZA201708498B (ru) |
Families Citing this family (169)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013066438A2 (en) | 2011-07-22 | 2013-05-10 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| ES2757623T3 (es) * | 2012-07-25 | 2020-04-29 | Broad Inst Inc | Proteínas de unión a ADN inducibles y herramientas de perturbación genómica y aplicaciones de las mismas |
| BR112015013784A2 (pt) | 2012-12-12 | 2017-07-11 | Massachusetts Inst Technology | aplicação, manipulação e otimização de sistemas, métodos e composições para manipulação de sequência e aplicações terapêuticas |
| EP2931892B1 (en) | 2012-12-12 | 2018-09-12 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
| EP3011029B1 (en) | 2013-06-17 | 2019-12-11 | The Broad Institute, Inc. | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
| WO2014204727A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| CN107995927B (zh) | 2013-06-17 | 2021-07-30 | 布罗德研究所有限公司 | 用于肝靶向和治疗的crispr-cas系统、载体和组合物的递送与用途 |
| KR20160034901A (ko) | 2013-06-17 | 2016-03-30 | 더 브로드 인스티튜트, 인코퍼레이티드 | 서열 조작에 최적화된 ｃｒｉｓｐｒ-ｃａｓ 이중 닉카아제 시스템, 방법 및 조성물 |
| CN105793425B (zh) | 2013-06-17 | 2021-10-26 | 布罗德研究所有限公司 | 使用病毒组分靶向障碍和疾病的crispr-cas系统和组合物的递送、用途和治疗应用 |
| US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | President And Fellows Of Harvard College | Methods for identifying a target site of a cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| US9340799B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | MRNA-sensing switchable gRNAs |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| AU2014361784A1 (en) * | 2013-12-12 | 2016-06-23 | Massachusetts Institute Of Technology | Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for HBV and viral diseases and disorders |
| WO2015089486A2 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
| KR20160089527A (ko) | 2013-12-12 | 2016-07-27 | 더 브로드 인스티튜트, 인코퍼레이티드 | 게놈 편집을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 조성물의 전달, 용도 및 치료적 응용 |
| US9068179B1 (en) | 2013-12-12 | 2015-06-30 | President And Fellows Of Harvard College | Methods for correcting presenilin point mutations |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| CA2932472A1 (en) | 2013-12-12 | 2015-06-18 | Massachusetts Institute Of Technology | Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders |
| US9725710B2 (en) | 2014-01-08 | 2017-08-08 | Flodesign Sonics, Inc. | Acoustophoresis device with dual acoustophoretic chamber |
| EP4063503A1 (en) | 2014-02-11 | 2022-09-28 | The Regents of the University of Colorado, a body corporate | Crispr enabled multiplexed genome engineering |
| WO2016022363A2 (en) | 2014-07-30 | 2016-02-11 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| AU2015342749B2 (en) | 2014-11-07 | 2022-01-27 | Editas Medicine, Inc. | Methods for improving CRISPR/Cas-mediated genome-editing |
| EP3985115A1 (en) | 2014-12-12 | 2022-04-20 | The Broad Institute, Inc. | Protected guide rnas (pgrnas) |
| AU2016226077B2 (en) | 2015-03-03 | 2021-12-23 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases with altered PAM specificity |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| US11390884B2 (en) | 2015-05-11 | 2022-07-19 | Editas Medicine, Inc. | Optimized CRISPR/cas9 systems and methods for gene editing in stem cells |
| KR20180031671A (ko) | 2015-06-09 | 2018-03-28 | 에디타스 메디신, 인코포레이티드 | 이식의 개선을 위한 crispr/cas-관련 방법 및 조성물 |
| MX2017016289A (es) | 2015-06-18 | 2018-08-15 | Broad Inst Inc | Mutaciones de la enzima crispr que reducen los efectos fuera del blanco. |
| WO2016205759A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation |
| EP3313989A4 (en) | 2015-06-29 | 2018-12-05 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
| CN114875012A (zh) * | 2015-08-28 | 2022-08-09 | 通用医疗公司 | 工程化的CRISPR-Cas9核酸酶 |
| WO2017053879A1 (en) | 2015-09-24 | 2017-03-30 | Editas Medicine, Inc. | Use of exonucleases to improve crispr/cas-mediated genome editing |
| IL294014B2 (en) | 2015-10-23 | 2024-07-01 | Harvard College | Nucleobase editors and their uses |
| EP3377626A1 (en) * | 2015-11-20 | 2018-09-26 | Life Technologies Corporation | Stabilized reagents for genome modification |
| WO2017165862A1 (en) | 2016-03-25 | 2017-09-28 | Editas Medicine, Inc. | Systems and methods for treating alpha 1-antitrypsin (a1at) deficiency |
| EP3433363A1 (en) | 2016-03-25 | 2019-01-30 | Editas Medicine, Inc. | Genome editing systems comprising repair-modulating enzyme molecules and methods of their use |
| US11236313B2 (en) | 2016-04-13 | 2022-02-01 | Editas Medicine, Inc. | Cas9 fusion molecules, gene editing systems, and methods of use thereof |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| US10337051B2 (en) | 2016-06-16 | 2019-07-02 | The Regents Of The University Of California | Methods and compositions for detecting a target RNA |
| LT3474669T (lt) | 2016-06-24 | 2022-06-10 | The Regents Of The University Of Colorado, A Body Corporate | Barkodu pažymėtų kombinatorinių bibliotekų generavimo būdai |
| WO2018005873A1 (en) * | 2016-06-29 | 2018-01-04 | The Broad Institute Inc. | Crispr-cas systems having destabilization domain |
| CA3032699A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harvard College | Adenosine nucleobase editors and uses thereof |
| US11078481B1 (en) | 2016-08-03 | 2021-08-03 | KSQ Therapeutics, Inc. | Methods for screening for cancer targets |
| AU2017308889B2 (en) | 2016-08-09 | 2023-11-09 | President And Fellows Of Harvard College | Programmable Cas9-recombinase fusion proteins and uses thereof |
| KR101710026B1 (ko) | 2016-08-10 | 2017-02-27 | 주식회사 무진메디 | Cas9 단백질 및 가이드 RNA의 혼성체를 함유하는 나노 리포좀 전달체 조성물 |
| US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| US11078483B1 (en) | 2016-09-02 | 2021-08-03 | KSQ Therapeutics, Inc. | Methods for measuring and improving CRISPR reagent function |
| WO2018064352A1 (en) | 2016-09-30 | 2018-04-05 | The Regents Of The University Of California | Rna-guided nucleic acid modifying enzymes and methods of use thereof |
| GB2569733B (en) | 2016-09-30 | 2022-09-14 | Univ California | RNA-guided nucleic acid modifying enzymes and methods of use thereof |
| US11242542B2 (en) * | 2016-10-07 | 2022-02-08 | Integrated Dna Technologies, Inc. | S. pyogenes Cas9 mutant genes and polypeptides encoded by same |
| WO2018068053A2 (en) | 2016-10-07 | 2018-04-12 | Integrated Dna Technologies, Inc. | S. pyogenes cas9 mutant genes and polypeptides encoded by same |
| WO2018071868A1 (en) | 2016-10-14 | 2018-04-19 | President And Fellows Of Harvard College | Aav delivery of nucleobase editors |
| SG10201913505WA (en) * | 2016-10-17 | 2020-02-27 | Univ Nanyang Tech | Truncated crispr-cas proteins for dna targeting |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| EP4095263A1 (en) | 2017-01-06 | 2022-11-30 | Editas Medicine, Inc. | Methods of assessing nuclease cleavage |
| IT201700016321A1 (it) * | 2017-02-14 | 2018-08-14 | Univ Degli Studi Di Trento | Mutanti di cas9 ad alta specificita' e loro applicazioni. |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | 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 | シトシンからグアニンへの塩基編集因子 |
| WO2018170184A1 (en) | 2017-03-14 | 2018-09-20 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| IL269458B2 (en) | 2017-03-23 | 2024-02-01 | Harvard College | Nucleic base editors that include nucleic acid programmable DNA binding proteins |
| JP2020515258A (ja) * | 2017-03-31 | 2020-05-28 | アジェノビア コーポレーション | 抗ウイルス治療剤 |
| US11732251B2 (en) | 2017-04-24 | 2023-08-22 | Dupont Nutrition Biosciences Aps | Anti-CRISPR polynucleotides and polypeptides and methods of use |
| CN108795989A (zh) * | 2017-04-26 | 2018-11-13 | 哈尔滨工业大学 | SpyCas9的基因编辑活性抑制位点及其抑制剂 |
| EP3615672A1 (en) | 2017-04-28 | 2020-03-04 | Editas Medicine, Inc. | Methods and systems for analyzing guide rna molecules |
| US11591601B2 (en) | 2017-05-05 | 2023-02-28 | The Broad Institute, Inc. | Methods for identification and modification of lncRNA associated with target genotypes and phenotypes |
| EP3622070A2 (en) * | 2017-05-10 | 2020-03-18 | Editas Medicine, Inc. | Crispr/rna-guided nuclease systems and methods |
| WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
| CN110662835B (zh) * | 2017-05-19 | 2023-04-28 | 清华大学 | 工程化改造用于由增强的指导RNA优化的基因编辑和转录调节的最小化SaCas9 CRISPR/Cas系统 |
| KR102151064B1 (ko) * | 2017-05-24 | 2020-09-02 | 기초과학연구원 | 매칭된 5' 뉴클레오타이드를 포함하는 가이드 rna를 포함하는 유전자 교정용 조성물 및 이를 이용한 유전자 교정 방법 |
| GB201708662D0 (en) * | 2017-05-31 | 2017-07-12 | Tropic Biosciences Uk Ltd | Compositions and methods for increasing shelf-life of banana |
| CN110770342B (zh) * | 2017-06-08 | 2023-11-17 | 国立大学法人大阪大学 | Dna被编辑了的真核细胞的制造方法、和在该方法中使用的试剂盒 |
| CN110997908A (zh) * | 2017-06-09 | 2020-04-10 | 爱迪塔斯医药公司 | 工程化的cas9核酸酶 |
| CN107365793A (zh) * | 2017-06-19 | 2017-11-21 | 百格基因科技（江苏）有限公司 | 一种适用于植物的大规模基因组编辑的方法 |
| US10011849B1 (en) | 2017-06-23 | 2018-07-03 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| US9982279B1 (en) | 2017-06-23 | 2018-05-29 | Inscripta, Inc. | Nucleic acid-guided nucleases |
| US20200140896A1 (en) * | 2017-06-30 | 2020-05-07 | Novartis Ag | Methods for the treatment of disease with gene editing systems |
| BR112020000310A2 (pt) * | 2017-07-07 | 2020-07-14 | Toolgen Incorporated | variantes de crispr alvo específicas |
| US11866726B2 (en) | 2017-07-14 | 2024-01-09 | Editas Medicine, Inc. | Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites |
| JP2020534795A (ja) | 2017-07-28 | 2020-12-03 | 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 | ファージによって支援される連続的進化（ｐａｃｅ）を用いて塩基編集因子を進化させるための方法および組成物 |
| JP7159288B2 (ja) * | 2017-07-28 | 2022-10-24 | ローカス アイピー カンパニー、エルエルシー | 皮膚、毛髪及び頭皮の健康を改善する酵母ベースのマスク |
| EP3662065A4 (en) * | 2017-08-04 | 2021-04-21 | Syngenta Participations AG | METHODS AND COMPOSITIONS FOR TARGETED GENOMIC INSERTION |
| AU2018320865B2 (en) | 2017-08-23 | 2023-09-14 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases with altered PAM specificity |
| US11319532B2 (en) | 2017-08-30 | 2022-05-03 | President And Fellows Of Harvard College | High efficiency base editors comprising Gam |
| WO2019051419A1 (en) * | 2017-09-08 | 2019-03-14 | University Of North Texas Health Science Center | MODIFIED CASE VARIANTS9 |
| US11572574B2 (en) | 2017-09-28 | 2023-02-07 | Toolgen Incorporated | Artificial genome manipulation for gene expression regulation |
| CN107630018B (zh) * | 2017-09-30 | 2018-10-12 | 深圳三智医学科技有限公司 | 一种用于编辑或修复hbb基因的试剂盒 |
| US11795443B2 (en) | 2017-10-16 | 2023-10-24 | The Broad Institute, Inc. | Uses of adenosine base editors |
| WO2019079462A1 (en) * | 2017-10-17 | 2019-04-25 | President And Fellows Of Harvard College | TRANSCRIPTION MODULATION SYSTEMS BASED ON CAS9 |
| SG11202003863VA (en) | 2017-11-01 | 2020-05-28 | Univ California | Casz compositions and methods of use |
| WO2019089808A1 (en) * | 2017-11-01 | 2019-05-09 | The Regents Of The University Of California | Class 2 crispr/cas compositions and methods of use |
| WO2019102381A1 (en) | 2017-11-21 | 2019-05-31 | Casebia Therapeutics Llp | Materials and methods for treatment of autosomal dominant retinitis pigmentosa |
| KR102387830B1 (ko) * | 2017-11-22 | 2022-04-18 | 고쿠리츠다이가쿠호진 고베다이가쿠 | 안정하고 부작용이 적은 게놈 편집용 복합체 및 이를 코딩하는 핵산 |
| KR102439221B1 (ko) | 2017-12-14 | 2022-09-01 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| US20210371877A1 (en) * | 2017-12-18 | 2021-12-02 | Spark Therapeutics, Inc. | Adeno-associated virus (aav) vector lipid nanoparticle compositions and methods of use |
| CN108048405A (zh) * | 2018-01-15 | 2018-05-18 | 上海市东方医院 | 稳定表达人内源性INav的细胞模型及其制备方法和用途 |
| KR20200124702A (ko) | 2018-02-23 | 2020-11-03 | 파이어니어 하이 부렛드 인터내쇼날 인코포레이팃드 | 신규한 cas9 오르소로그 |
| AU2019236209A1 (en) | 2018-03-14 | 2020-10-01 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| JP7550648B2 (ja) * | 2018-03-19 | 2024-09-13 | クリスパー セラピューティクス アーゲー | 新規ｒｎａプログラム可能エンドヌクレアーゼ系およびその使用 |
| JP2021519073A (ja) * | 2018-03-29 | 2021-08-10 | ジェネンテック， インコーポレイテッド | 哺乳動物細胞におけるラクトジェニック活性の制御 |
| US20190336585A1 (en) * | 2018-05-03 | 2019-11-07 | John Lawrence Mee | Method for sustainable human cognitive enhancement |
| WO2019222423A1 (en) * | 2018-05-15 | 2019-11-21 | The Brigham And Women's Hospital, Inc. | Compositions and methods related to tumor cell killers and vaccines |
| AU2019281158A1 (en) * | 2018-06-08 | 2021-01-14 | Modalis Therapeutics Corporation | Modified Cas9 protein and use thereof |
| WO2019235907A1 (ko) * | 2018-06-08 | 2019-12-12 | 충남대학교 산학협력단 | Crispr/cas9 시스템을 이용하여 플라보노이드 생합성 유전체를 편집하기 위한 조성물 및 이의 이용 |
| CN110684755B (zh) * | 2018-07-05 | 2021-12-31 | 清华大学 | 基于进化信息构建嵌合SaCas9用于增强和扩展PAM位点的识别 |
| US20210261957A1 (en) | 2018-07-10 | 2021-08-26 | Alia Therapeutics S.R.L. | Vesicles for traceless delivery of guide rna molecules and/or guide rna molecule/rna-guided nuclease complex(es) and a production method thereof |
| WO2020028729A1 (en) | 2018-08-01 | 2020-02-06 | Mammoth Biosciences, Inc. | Programmable nuclease compositions and methods of use thereof |
| CN108949830B (zh) * | 2018-08-03 | 2021-11-26 | 福州大学 | 一种在鱼类中实现基因组编辑、精确定点基因敲入的方法 |
| CA3109956A1 (en) * | 2018-08-24 | 2020-02-27 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for the modification of plants |
| CN109402115B (zh) * | 2018-09-06 | 2024-02-02 | 广州普世利华科技有限公司 | 靶向Rett突变基因RNA的gRNA及Rett突变基因的检测方法、检测试剂盒 |
| EP3847251A1 (en) * | 2018-09-07 | 2021-07-14 | Astrazeneca AB | Compositions and methods for improved nucleases |
| US20210340568A1 (en) * | 2018-10-09 | 2021-11-04 | The University Of North Carolina At Chapel Hill | Regulated gene editing system |
| EP3880826A4 (en) * | 2018-11-07 | 2022-08-24 | Akouos, Inc. | USE OF ADENO-ASSOCIATED VIRAL VECTORS TO CORRECT GENE DEFECTS/EXPRESS PROTEINS IN CILIATE AND SUPPORTING CELLS IN THE INNER EAR |
| CN113330023A (zh) * | 2018-11-08 | 2021-08-31 | 代表亚利桑那州立大学的亚利桑那校董会 | 体内具有crispr超级阻遏子的合成免疫调控 |
| CN109385425A (zh) * | 2018-11-13 | 2019-02-26 | 中山大学 | 一种高特异性ABE碱基编辑系统及其在β血红蛋白病中的应用 |
| WO2020106771A1 (en) * | 2018-11-19 | 2020-05-28 | Exosome Therapeutics, Inc. | Compositions and methods for producing exosome loaded therapeutics for the treatment of multiple oncological disorders |
| JP2022514493A (ja) * | 2018-12-14 | 2022-02-14 | パイオニア ハイ－ブレッド インターナショナル， インコーポレイテッド | ゲノム編集のための新規なｃｒｉｓｐｒ－ｃａｓシステム |
| CN111321171A (zh) * | 2018-12-14 | 2020-06-23 | 江苏集萃药康生物科技有限公司 | 一种应用CRISPR/Cas9介导ES打靶技术制备基因打靶动物模型的方法 |
| EP3931313A2 (en) | 2019-01-04 | 2022-01-05 | Mammoth Biosciences, Inc. | Programmable nuclease improvements and compositions and methods for nucleic acid amplification and detection |
| US20220098572A1 (en) * | 2019-01-31 | 2022-03-31 | Beam Therapeutics Inc. | Nucleobase editors having reduced non-target deamination and assays for characterizing nucleobase editors |
| US10982200B2 (en) | 2019-02-14 | 2021-04-20 | Metagenomi Ip Technologies, Llc | Enzymes with RuvC domains |
| EP3938499A1 (en) * | 2019-03-12 | 2022-01-19 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Cas9 variants with enhanced specificity |
| DE112020001342T5 (de) | 2019-03-19 | 2022-01-13 | President and Fellows of Harvard College | Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen |
| CN110009626A (zh) * | 2019-04-11 | 2019-07-12 | 北京百度网讯科技有限公司 | 用于生成图像的方法和装置 |
| SG11202111427RA (en) | 2019-05-28 | 2021-11-29 | Astellas Pharma Inc | Method for treating muscular dystrophy by targeting dmpk gene |
| US20210008161A1 (en) | 2019-06-17 | 2021-01-14 | Crispr Therapeutics Ag | Methods and compositions for improved homology directed repair |
| CN110272881B (zh) * | 2019-06-29 | 2021-04-30 | 复旦大学 | 核酸内切酶SpCas9高特异性截短变异体TSpCas9-V1/V2及其应用 |
| CN114096667A (zh) * | 2019-07-08 | 2022-02-25 | 因思科瑞普特公司 | 经由LexA-Rad51融合蛋白增加核酸指导的细胞编辑 |
| US20220315914A1 (en) * | 2019-07-08 | 2022-10-06 | The Regents Of The University Of California | Variant type v crispr/cas effector polypeptides and methods of use thereof |
| CN110600075B (zh) * | 2019-08-14 | 2021-08-03 | 浙江工业大学 | 一种基于配体生长策略的蛋白质atp对接方法 |
| CN110402852A (zh) * | 2019-08-28 | 2019-11-05 | 浙江海洋大学 | 利于提高虎斑乌贼产卵数量与质量的养殖方法 |
| AR120302A1 (es) * | 2019-11-01 | 2022-02-09 | Syngenta Crop Protection Ag | Métodos de control de malezas y composiciones y plantas relacionadas |
| KR102493904B1 (ko) * | 2019-12-13 | 2023-01-31 | 한국생명공학연구원 | EeCpf1에 의해 IL2Rg 유전자가 돌연변이된 면역부전 동물모델 및 그 제조방법 |
| CN111337666B (zh) * | 2020-02-12 | 2021-04-02 | 山东大学 | I-motif重组介导的FRET探针及其原位成像癌细胞表面蛋白质同源二聚化的应用 |
| WO2021163515A1 (en) * | 2020-02-12 | 2021-08-19 | Temple University - Of The Commonwealth System Of Higher Education | Crispr-cas9 mediated disruption of alcam gene inhibits adhesion and trans-endothelial migration of myeloid cells |
| IL294120B2 (en) * | 2020-03-11 | 2023-10-01 | Sigma Aldrich Co Llc | SPCAS9 nucleases with high replication fidelity for genome modification |
| EP4118203A4 (en) * | 2020-03-11 | 2024-03-27 | The Broad Institute, Inc. | NEW ENZYMES CASES AND METHODS FOR SPECIFICITY AND ACTIVITY PROFILING |
| WO2021202559A1 (en) * | 2020-03-31 | 2021-10-07 | Metagenomi Ip Technologies, Llc | Class ii, type ii crispr systems |
| KR20220161383A (ko) | 2020-03-31 | 2022-12-06 | 메타지노미, 인크. | 클래스 ii, 유형 ii crispr 시스템 |
| DE112021002672T5 (de) | 2020-05-08 | 2023-04-13 | President And Fellows Of Harvard College | Vefahren und zusammensetzungen zum gleichzeitigen editieren beider stränge einer doppelsträngigen nukleotid-zielsequenz |
| WO2022018638A1 (en) | 2020-07-21 | 2022-01-27 | Crispr Therapeutics Ag | Genome-editing compositions and methods to modulate faah for treatment of neurological disorders |
| CN111904973B (zh) * | 2020-07-27 | 2021-12-03 | 中国农业科学院兰州兽医研究所 | ssc-miR-122在制备调节猪繁殖与呼吸综合征病毒复制的药物中的应用 |
| CN111979273B (zh) * | 2020-08-24 | 2022-05-27 | 苏州启辰生物科技有限公司 | 一种制备人源化ace2小鼠模型的方法 |
| WO2022047194A1 (en) * | 2020-08-28 | 2022-03-03 | Rau Bio Limited | Approaches to simulating the interactions of biological systems through the use of modular computational workflows |
| WO2022087135A1 (en) * | 2020-10-21 | 2022-04-28 | Emendobio Inc. | Novel omni 56, 58, 65, 68, 71, 75, 78, and 84 crispr nucleases |
| WO2022109058A1 (en) * | 2020-11-18 | 2022-05-27 | Entrada Therapeutics, Inc. | Nucleases comprising cell penetrating peptide sequences |
| EP4256045A1 (en) * | 2020-12-02 | 2023-10-11 | The Regents of the University of California | Crispr-cas effector polypeptides and methods of use thereof |
| WO2022133246A1 (en) | 2020-12-17 | 2022-06-23 | Vertex Pharmaceuticals Incorporated | Compositions and methods for editing beta-globin for treatment of hemaglobinopathies |
| CN114807240B (zh) * | 2021-01-21 | 2024-02-06 | 深圳市第二人民医院(深圳市转化医学研究院) | 一种连接有适配体的模板分子及其试剂盒 |
| JP2024510604A (ja) * | 2021-03-11 | 2024-03-08 | エメンドバイオ・インコーポレイテッド | Ｃ３セーフハーバー部位へのノックイン戦略 |
| CN113249384A (zh) * | 2021-04-27 | 2021-08-13 | 重庆医科大学 | 可靶向编辑HBV cccDNA的特异sgRNA序列及其应用 |
| WO2022238958A1 (en) | 2021-05-12 | 2022-11-17 | Crispr Therapeutics Ag | Multiplex gene editing |
| JP2024525028A (ja) * | 2021-06-29 | 2024-07-09 | カウンスィル オブ サイエンティフィック アンド インダストリアル リサーチ | 操作されたＦｎＣａｓ９およびその使用 |
| CN113584049B (zh) * | 2021-07-27 | 2023-02-03 | 杭州师范大学 | Vdac1基因在调控植物开花期中的应用 |
| CN113755498A (zh) * | 2021-09-27 | 2021-12-07 | 赛业（苏州）生物科技有限公司 | 靶向小鼠Ube3a基因的gRNA及构建AS疾病小鼠模型的方法 |
| IL312452A (en) | 2021-11-01 | 2024-06-01 | Tome Biosciences Inc | A transformant has a single structure for the simultaneous transfer of a gene editing mechanism and a nucleic acid cargo |
| CN114214330A (zh) * | 2021-12-20 | 2022-03-22 | 杭州百凌生物科技有限公司 | 一种检测脊索瘤的质控品及其制备方法和应用 |
| AU2022420615A1 (en) | 2021-12-22 | 2024-07-04 | Tome Biosciences, Inc. | Co-delivery of a gene editor construct and a donor template |
| WO2023205744A1 (en) | 2022-04-20 | 2023-10-26 | Tome Biosciences, Inc. | Programmable gene insertion compositions |
| WO2023215831A1 (en) | 2022-05-04 | 2023-11-09 | Tome Biosciences, Inc. | Guide rna compositions for programmable gene insertion |
| WO2023219933A1 (en) | 2022-05-09 | 2023-11-16 | Entrada Therapeutics, Inc. | Compositions and methods for delivery of nucleic acid therapeutics |
| WO2023225670A2 (en) | 2022-05-20 | 2023-11-23 | Tome Biosciences, Inc. | Ex vivo programmable gene insertion |
| WO2024020587A2 (en) | 2022-07-22 | 2024-01-25 | Tome Biosciences, Inc. | Pleiopluripotent stem cell programmable gene insertion |
| WO2024138194A1 (en) | 2022-12-22 | 2024-06-27 | Tome Biosciences, Inc. | Platforms, compositions, and methods for in vivo programmable gene insertion |
| CN116376975B (zh) * | 2023-02-27 | 2024-05-14 | 中国科学院脑科学与智能技术卓越创新中心 | 激活异染色质基因的方法及应用 |
| CN116987730B (zh) * | 2023-09-22 | 2023-12-01 | 西北农林科技大学深圳研究院 | 硫氧还蛋白StCDSP32在植物抗病中的应用 |
Family Cites Families (185)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS501A (ru) | 1973-04-28 | 1975-01-06 | ||
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US7150982B2 (en) | 1991-09-09 | 2006-12-19 | Third Wave Technologies, Inc. | RNA detection assays |
| US5593972A (en) | 1993-01-26 | 1997-01-14 | The Wistar Institute | Genetic immunization |
| US5543158A (en) | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
| US6007845A (en) | 1994-07-22 | 1999-12-28 | Massachusetts Institute Of Technology | Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers |
| US7745416B2 (en) | 1995-04-11 | 2010-06-29 | The Regents Of The University Of California | Method for in vivo regulation of cardiac muscle contractility |
| US5622856A (en) | 1995-08-03 | 1997-04-22 | Avigen | High efficiency helper system for AAV vector production |
| US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
| US5855913A (en) | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US5846946A (en) | 1996-06-14 | 1998-12-08 | Pasteur Merieux Serums Et Vaccins | Compositions and methods for administering Borrelia DNA |
| US5944710A (en) | 1996-06-24 | 1999-08-31 | Genetronics, Inc. | Electroporation-mediated intravascular delivery |
| US5869326A (en) | 1996-09-09 | 1999-02-09 | Genetronics, Inc. | Electroporation employing user-configured pulsing scheme |
| GB9907461D0 (en) | 1999-03-31 | 1999-05-26 | King S College London | Neurite regeneration |
| GB9710049D0 (en) | 1997-05-19 | 1997-07-09 | Nycomed Imaging As | Method |
| US6251677B1 (en) | 1997-08-25 | 2001-06-26 | The Trustees Of The University Of Pennsylvania | Hybrid adenovirus-AAV virus and methods of use thereof |
| GB9720465D0 (en) | 1997-09-25 | 1997-11-26 | Oxford Biomedica Ltd | Dual-virus vectors |
| CN100342008C (zh) | 1997-10-24 | 2007-10-10 | 茵维特罗根公司 | 利用具重组位点的核酸进行重组克隆 |
| US7868149B2 (en) | 1999-07-20 | 2011-01-11 | Monsanto Technology Llc | Plant genome sequence and uses thereof |
| US6603061B1 (en) | 1999-07-29 | 2003-08-05 | Monsanto Company | Agrobacterium-mediated plant transformation method |
| GB0024550D0 (ru) | 2000-10-06 | 2000-11-22 | Oxford Biomedica Ltd | |
| WO2002074968A1 (en) | 2001-03-16 | 2002-09-26 | Naoya Kobayashi | Method for proliferating a liver cell, a liver cell obtained thereby, and use thereof |
| ES2404689T3 (es) | 2001-04-05 | 2013-05-28 | The Johns Hopkins University | Vacunas quiméricas que comprenden el dominio lumenal de LAMP-1 o LAMP-2 |
| BR0211111A (pt) | 2001-07-12 | 2004-06-22 | Univ Massachusetts | Molécula de ácido nucleico isolada, vetor, célula hospedeira, transgene, precursor de rna engenheirado, animal transgênico não humano, e, método de induzir a interferência de ácido ribonucleico de um gene alvo em uma célula |
| AU2002327430A1 (en) | 2001-08-08 | 2003-02-24 | Genzyme Corporation | Methods for treating diabetes and other blood sugar disorders |
| WO2003016338A1 (en) | 2001-08-15 | 2003-02-27 | Parker Hughes Institute | Crystal structure of the btk kinase domain |
| GB0125216D0 (en) | 2001-10-19 | 2001-12-12 | Univ Strathclyde | Dendrimers for use in targeted delivery |
| US20090100536A1 (en) | 2001-12-04 | 2009-04-16 | Monsanto Company | Transgenic plants with enhanced agronomic traits |
| AU2002353231B2 (en) | 2001-12-21 | 2008-10-16 | Oxford Biomedica (Uk) Limited | Method for producing a transgenic organism using a lentiviral expression vector such as EIAV |
| US7539579B2 (en) | 2002-04-09 | 2009-05-26 | Beattie Kenneth L | Oligonucleotide probes for genosensor chips |
| WO2003104414A2 (en) | 2002-06-11 | 2003-12-18 | The Scripps Research Institute | Artificial transcription factors |
| DK1519714T3 (da) | 2002-06-28 | 2011-01-31 | Protiva Biotherapeutics Inc | Fremgangsmåde og apparat til fremstilling af liposomer |
| GB0220467D0 (en) | 2002-09-03 | 2002-10-09 | Oxford Biomedica Ltd | Composition |
| WO2004029219A2 (en) | 2002-09-27 | 2004-04-08 | Cold Spring Harbor Laboratory | Cell-based rna interference and related methods and compositions |
| AU2003290937A1 (en) | 2002-11-15 | 2004-06-15 | Trustees Of Boston University | Cis/trans riboregulators |
| US20060178297A1 (en) | 2003-01-28 | 2006-08-10 | Troy Carol M | Systems and methods for silencing expression of a gene in a cell and uses thereof |
| JP2007524399A (ja) | 2003-07-03 | 2007-08-30 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 機能性ｄｎａエレメントおよび細胞性タンパク質のゲノムマッピング |
| EP2567693B1 (en) | 2003-07-16 | 2015-10-21 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering RNA |
| CA2534296C (en) | 2003-08-08 | 2013-03-26 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| US7803397B2 (en) | 2003-09-15 | 2010-09-28 | Protiva Biotherapeutics, Inc. | Polyethyleneglycol-modified lipid compounds and uses thereof |
| GB0325379D0 (en) | 2003-10-30 | 2003-12-03 | Oxford Biomedica Ltd | Vectors |
| FR2862659B1 (fr) | 2003-11-21 | 2006-02-10 | Pasteur Institut | Genome de legionella pneumophila souche paris- applications diagnostiques et epidemiologiques |
| US8053232B2 (en) | 2004-01-23 | 2011-11-08 | Virxsys Corporation | Correction of alpha-1-antitrypsin genetic defects using spliceosome mediated RNA trans splicing |
| WO2005074511A2 (en) | 2004-01-27 | 2005-08-18 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for homozygous gene inactivation using collections of pre-defined nucleotide sequences complementary to chromosomal transcripts |
| US20050220796A1 (en) | 2004-03-31 | 2005-10-06 | Dynan William S | Compositions and methods for modulating DNA repair |
| ATE537263T1 (de) | 2004-06-07 | 2011-12-15 | Protiva Biotherapeutics Inc | Kationische lipide und verwendungsverfahren |
| AU2005252273B2 (en) | 2004-06-07 | 2011-04-28 | Arbutus Biopharma Corporation | Lipid encapsulated interfering RNA |
| FR2872170B1 (fr) | 2004-06-25 | 2006-11-10 | Centre Nat Rech Scient Cnrse | Lentivirus non interactif et non replicatif, preparation et utilisations |
| AU2005274948B2 (en) | 2004-07-16 | 2011-09-22 | Genvec, Inc. | Vaccines against aids comprising CMV/R-nucleic acid constructs |
| GB0422877D0 (en) | 2004-10-14 | 2004-11-17 | Univ Glasgow | Bioactive polymers |
| US20070081982A1 (en) | 2005-04-28 | 2007-04-12 | Elisabeth Evertsz | Multiple RNAi expression cassettes for simultaneous delivery of RNAi agents related to heterozygotic expression patterns |
| US7892224B2 (en) | 2005-06-01 | 2011-02-22 | Brainlab Ag | Inverse catheter planning |
| SG10201508995QA (en) | 2005-07-26 | 2015-11-27 | Sangamo Biosciences Inc | Targeted integration and expression of exogenous nucleic acid sequences |
| WO2007025097A2 (en) | 2005-08-26 | 2007-03-01 | Danisco A/S | Use |
| WO2007048046A2 (en) | 2005-10-20 | 2007-04-26 | Protiva Biotherapeutics, Inc. | Sirna silencing of filovirus gene expression |
| ES2377660T3 (es) | 2005-10-28 | 2012-03-29 | Mitsubishi Tanabe Pharma Corporation | Nuevo péptido que penetra en las células |
| US8101741B2 (en) | 2005-11-02 | 2012-01-24 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| GB0526211D0 (en) | 2005-12-22 | 2006-02-01 | Oxford Biomedica Ltd | Viral vectors |
| WO2007091269A2 (en) | 2006-02-08 | 2007-08-16 | Quark Pharmaceuticals, Inc. | NOVEL TANDEM siRNAS |
| EP1994182B1 (en) | 2006-03-15 | 2019-05-29 | Siemens Healthcare Diagnostics Inc. | Degenerate nucleobase analogs |
| CN103614375A (zh) | 2006-05-11 | 2014-03-05 | 阿尔尼拉姆医药品有限公司 | 抑制pcsk9基因表达的组合物和方法 |
| WO2008054544A2 (en) | 2006-05-22 | 2008-05-08 | Immune Disease Institute, Inc. | Method for delivery across the blood brain barrier |
| US7915399B2 (en) | 2006-06-09 | 2011-03-29 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| JP2008078613A (ja) | 2006-08-24 | 2008-04-03 | Rohm Co Ltd | 窒化物半導体の製造方法及び窒化物半導体素子 |
| WO2008093152A1 (en) | 2007-02-01 | 2008-08-07 | Cellectis | Obligate heterodimer meganucleases and uses thereof |
| PL2126130T3 (pl) | 2007-03-02 | 2015-10-30 | Dupont Nutrition Biosci Aps | Hodowle o ulepszonej fagooporności |
| PE20090064A1 (es) | 2007-03-26 | 2009-03-02 | Novartis Ag | Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende |
| WO2008149176A1 (en) | 2007-06-06 | 2008-12-11 | Cellectis | Meganuclease variants cleaving a dna target sequence from the mouse rosa26 locus and uses thereof |
| AU2008346801A1 (en) | 2007-12-31 | 2009-07-16 | Nanocor Therapeutics, Inc. | RNA interference for the treatment of heart failure |
| US20100081707A1 (en) | 2008-02-21 | 2010-04-01 | Ali Robin R | Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea |
| HUE034483T2 (en) | 2008-04-15 | 2018-02-28 | Protiva Biotherapeutics Inc | New lipid preparations for introducing a nucleic acid |
| US8575305B2 (en) | 2008-06-04 | 2013-11-05 | Medical Research Council | Cell penetrating peptides |
| JP2011526619A (ja) | 2008-06-30 | 2011-10-13 | サイレンシード リミテッド | 局所ドラッグデリバリーシステム、その方法、および、その組成物 |
| EP2309980A1 (en) | 2008-07-08 | 2011-04-20 | S.I.F.I. Societa' Industria Farmaceutica Italiana | Ophthalmic compositions for treating pathologies of the posterior segment of the eye |
| WO2010011961A2 (en) | 2008-07-25 | 2010-01-28 | University Of Georgia Research Foundation, Inc. | Prokaryotic rnai-like system and methods of use |
| US20100076057A1 (en) | 2008-09-23 | 2010-03-25 | Northwestern University | TARGET DNA INTERFERENCE WITH crRNA |
| US9404098B2 (en) | 2008-11-06 | 2016-08-02 | University Of Georgia Research Foundation, Inc. | Method for cleaving a target RNA using a Cas6 polypeptide |
| CA2742954C (en) | 2008-11-07 | 2018-07-10 | Massachusetts Institute Of Technology | Aminoalcohol lipidoids and uses thereof |
| US20110016540A1 (en) | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Genome editing of genes associated with trinucleotide repeat expansion disorders in animals |
| EP3156494B8 (en) | 2008-12-04 | 2018-09-19 | Sangamo Therapeutics, Inc. | Genome editing in rats using zinc-finger nucleases |
| NZ593618A (en) | 2008-12-10 | 2013-02-22 | Alnylam Pharmaceuticals Inc | Gnaq targeted dsrna compositions and methods for inhibiting expression |
| WO2010075424A2 (en) | 2008-12-22 | 2010-07-01 | The Regents Of University Of California | Compositions and methods for downregulating prokaryotic genes |
| 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 |
| WO2011036510A1 (en) | 2009-09-24 | 2011-03-31 | Cellectis | Meganuclease variants cleaving the genome of the herpes simplex virus and uses thereof |
| KR20100133319A (ko) | 2009-06-11 | 2010-12-21 | 주식회사 툴젠 | 표적 특이적인 게놈의 재배열을 위한 표적 특이적 뉴클레아제 및 이의 용도 |
| WO2011000107A1 (en) | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for delivery of therapeutic agents to solid tumors |
| US8236943B2 (en) | 2009-07-01 | 2012-08-07 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
| JP2013500018A (ja) | 2009-07-24 | 2013-01-07 | シグマ−アルドリッチ・カンパニー・リミテッド・ライアビリティ・カンパニー | ゲノム編集のための方法 |
| US9234016B2 (en) | 2009-07-28 | 2016-01-12 | Sangamo Biosciences, Inc. | Engineered zinc finger proteins for treating trinucleotide repeat disorders |
| US8889394B2 (en) | 2009-09-07 | 2014-11-18 | Empire Technology Development Llc | Multiple domain proteins |
| EP2504439B1 (en) | 2009-11-27 | 2016-03-02 | BASF Plant Science Company GmbH | Optimized endonucleases and uses thereof |
| SG181823A1 (en) | 2009-12-23 | 2012-07-30 | Max Planck Gesellschaft | Influenza targets |
| CA2788850C (en) | 2010-02-09 | 2019-06-25 | Sangamo Biosciences, Inc. | Targeted genomic modification with partially single-stranded donor molecules |
| US10087431B2 (en) | 2010-03-10 | 2018-10-02 | The Regents Of The University Of California | Methods of generating nucleic acid fragments |
| US8771985B2 (en) | 2010-04-26 | 2014-07-08 | Sangamo Biosciences, Inc. | Genome editing of a Rosa locus using zinc-finger nucleases |
| US8927514B2 (en) | 2010-04-30 | 2015-01-06 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
| SG185481A1 (en) | 2010-05-10 | 2012-12-28 | Univ California | Endoribonuclease compositions and methods of use thereof |
| US8372951B2 (en) | 2010-05-14 | 2013-02-12 | National Tsing Hua University | Cell penetrating peptides for intracellular delivery |
| CA2798988C (en) | 2010-05-17 | 2020-03-10 | Sangamo Biosciences, Inc. | Tal-effector (tale) dna-binding polypeptides and uses thereof |
| CN102946907A (zh) | 2010-05-28 | 2013-02-27 | 牛津生物医学（英国）有限公司 | 慢病毒载体向脑的递送 |
| BR112013001685B1 (pt) | 2010-07-23 | 2021-10-13 | Sigma-Aldrich Co. Llc | Método para editar pelo menos uma sequência cromossômica endógena em uma célula pela inserção de uma sequência na sequência cromossômica |
| DK2601611T3 (da) | 2010-08-02 | 2021-02-01 | Integrated Dna Tech Inc | Fremgangsmåder til forudsigelse af stabilitet og smeltetemperaturer for nukleinsyreduplekser |
| US9193827B2 (en) | 2010-08-26 | 2015-11-24 | Massachusetts Institute Of Technology | Poly(beta-amino alcohols), their preparation, and uses thereof |
| WO2012031205A2 (en) | 2010-09-03 | 2012-03-08 | The Brigham And Women's Hospital, Inc. | Lipid-polymer hybrid particles |
| WO2012051343A1 (en) | 2010-10-12 | 2012-04-19 | The Children's Hospital Of Philadelphia | Methods and compositions for treating hemophilia b |
| PL2691443T3 (pl) | 2011-03-28 | 2021-08-30 | Massachusetts Institute Of Technology | Sprzężone lipomery i ich zastosowania |
| DE12722942T1 (de) | 2011-03-31 | 2021-09-30 | Modernatx, Inc. | Freisetzung und formulierung von manipulierten nukleinsäuren |
| SG194583A1 (en) | 2011-04-22 | 2013-12-30 | Univ California | Adeno-associated virus virions with variant capsid and methods of use thereof |
| BR112013025567B1 (pt) | 2011-04-27 | 2021-09-21 | Amyris, Inc | Métodos para modificação genômica |
| US20120295960A1 (en) | 2011-05-20 | 2012-11-22 | Oxford Biomedica (Uk) Ltd. | Treatment regimen for parkinson's disease |
| US20140113376A1 (en) | 2011-06-01 | 2014-04-24 | Rotem Sorek | Compositions and methods for downregulating prokaryotic genes |
| ES2961613T3 (es) | 2011-09-21 | 2024-03-12 | Sangamo Therapeutics Inc | Métodos y composiciones para la regulación de la expresión transgénica |
| JP2014530603A (ja) | 2011-10-06 | 2014-11-20 | サンガモ バイオサイエンシーズ， インコーポレイテッド | Ｈｉｖ感染を制御するための方法および組成物 |
| US20130122096A1 (en) | 2011-11-14 | 2013-05-16 | Silenseed Ltd. | Compositions for drug delivery and methods of manufacturing and using same |
| JP6259766B2 (ja) | 2011-11-18 | 2018-01-10 | ユニヴェルシテ ラヴァルＵｎｉｖｅｒｓｉｔｅ Ｌａｖａｌ | フラタキシンレベルを増加させる方法および生成物ならびにその使用 |
| US10640785B2 (en) | 2011-11-22 | 2020-05-05 | The Children's Hospital Of Philadelphia | Virus vectors for highly efficient transgene delivery |
| US8450107B1 (en) | 2011-11-30 | 2013-05-28 | The Broad Institute Inc. | Nucleotide-specific recognition sequences for designer TAL effectors |
| JP2015501844A (ja) | 2011-12-16 | 2015-01-19 | モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 修飾ヌクレオシド、ヌクレオチドおよび核酸組成物 |
| GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
| KR102084539B1 (ko) | 2012-02-29 | 2020-03-04 | 상가모 테라퓨틱스, 인코포레이티드 | 헌팅턴병을 치료하기 위한 방법 및 조성물 |
| 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 |
| AU2013204327B2 (en) | 2012-04-20 | 2016-09-01 | Aviagen | Cell transfection method |
| DE202013012241U1 (de) | 2012-05-25 | 2016-01-18 | Emmanuelle Charpentier | Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription |
| SG11201407970VA (en) | 2012-06-01 | 2014-12-30 | Univ Drexel | Modulation of hepatitis b virus cccdna transcription |
| US8614194B1 (en) | 2012-07-25 | 2013-12-24 | Kaohsiung Medical University | Anionic cell penetrating peptide and its use for intracellular delivery |
| DK2906684T3 (da) | 2012-10-10 | 2020-09-28 | Sangamo Therapeutics Inc | T-celle-modificerende forbindelser og anvendelser deraf |
| ES2926021T3 (es) * | 2012-10-23 | 2022-10-21 | Toolgen Inc | Composición para escindir un ADN objetivo que comprende un ARN guía específico para el ADN objetivo y ácido nucleico codificador de proteína Cas o proteína Cas, y uso de la misma |
| PL2928496T3 (pl) | 2012-12-06 | 2020-04-30 | Sigma-Aldrich Co. Llc | Modyfikacja i regulacja genomu w oparciu o CRISPR |
| WO2014093479A1 (en) | 2012-12-11 | 2014-06-19 | Montana State University | Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| PL2898075T3 (pl) | 2012-12-12 | 2016-09-30 | PROJEKTOWANIE i OPTYMALIZACJA ULEPSZONYCH SYSTEMÓW, SPOSOBY I KOMPOZYCJE ENZYMÓW DO MANIPULACJI SEKWENCJĄ | |
| WO2014093694A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes |
| BR112015013784A2 (pt) | 2012-12-12 | 2017-07-11 | Massachusetts Inst Technology | aplicação, manipulação e otimização de sistemas, métodos e composições para manipulação de sequência e aplicações terapêuticas |
| EP2931892B1 (en) | 2012-12-12 | 2018-09-12 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
| PL2896697T3 (pl) | 2012-12-12 | 2016-01-29 | Broad Inst Inc | Projektowanie systemów, sposoby i optymalizowane kompozycje kierujące do manipulacji sekwencją |
| MX2015007549A (es) | 2012-12-12 | 2017-01-20 | Broad Inst Inc | Modificaciones de sistemas, métodos y composiciones guía optimizadas para la manipulación de secuencias. |
| EP2931899A1 (en) | 2012-12-12 | 2015-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| US8993233B2 (en) | 2012-12-12 | 2015-03-31 | The Broad Institute Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
| EP2825654B1 (en) * | 2012-12-12 | 2017-04-26 | The Broad Institute, Inc. | Crispr-cas component systems, methods and compositions for sequence manipulation |
| RU2699523C2 (ru) | 2012-12-17 | 2019-09-05 | Президент Энд Фэллоуз Оф Харвард Коллидж | Рнк-направляемая инженерия генома человека |
| EP3919505B1 (en) | 2013-01-16 | 2023-08-30 | Emory University | Uses of cas9-nucleic acid complexes |
| WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
| WO2014124226A1 (en) | 2013-02-07 | 2014-08-14 | The Rockefeller University | Sequence specific antimicrobials |
| US9163837B2 (en) | 2013-02-27 | 2015-10-20 | Siemens Aktiengesellschaft | Flow conditioner in a combustor of a gas turbine engine |
| NZ712727A (en) | 2013-03-14 | 2017-05-26 | Caribou Biosciences Inc | Compositions and methods of nucleic acid-targeting nucleic acids |
| KR102210322B1 (ko) | 2013-03-15 | 2021-02-01 | 더 제너럴 하스피탈 코포레이션 | Rna-안내 게놈 편집의 특이성을 증가시키기 위한 rna-안내 foki 뉴클레아제(rfn)의 용도 |
| KR102109069B1 (ko) | 2013-03-27 | 2020-05-12 | 윌코아게 | 디바이스들을 인라인 검사 및/또는 테스트하는 방법 및 그와 같은 방법을 수행하는 장치 |
| ES2747833T3 (es) | 2013-04-04 | 2020-03-11 | Dartmouth College | Composiciones y procedimientos para la escisión in vivo del ADN proviral del vih-1 |
| CN116083487A (zh) | 2013-05-15 | 2023-05-09 | 桑格摩生物治疗股份有限公司 | 用于治疗遗传病状的方法和组合物 |
| WO2014191518A1 (en) | 2013-05-29 | 2014-12-04 | Cellectis | A method for producing precise dna cleavage using cas9 nickase activity |
| EP3003392B1 (en) | 2013-06-04 | 2019-10-23 | President and Fellows of Harvard College | Rna-guideded transcriptional regulation |
| US20140356956A1 (en) | 2013-06-04 | 2014-12-04 | President And Fellows Of Harvard College | RNA-Guided Transcriptional Regulation |
| AU2014274840B2 (en) | 2013-06-05 | 2020-03-12 | Duke University | RNA-guided gene editing and gene regulation |
| CN107995927B (zh) | 2013-06-17 | 2021-07-30 | 布罗德研究所有限公司 | 用于肝靶向和治疗的crispr-cas系统、载体和组合物的递送与用途 |
| ES2767318T3 (es) | 2013-06-17 | 2020-06-17 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para generar modelos y actuar sobre enfermedades y trastornos de células posmitóticas |
| EP3011029B1 (en) | 2013-06-17 | 2019-12-11 | The Broad Institute, Inc. | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
| CN105793425B (zh) | 2013-06-17 | 2021-10-26 | 布罗德研究所有限公司 | 使用病毒组分靶向障碍和疾病的crispr-cas系统和组合物的递送、用途和治疗应用 |
| KR20160034901A (ko) | 2013-06-17 | 2016-03-30 | 더 브로드 인스티튜트, 인코퍼레이티드 | 서열 조작에 최적화된 ｃｒｉｓｐｒ-ｃａｓ 이중 닉카아제 시스템, 방법 및 조성물 |
| WO2014204727A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| CN103343120B (zh) * | 2013-07-04 | 2015-03-04 | 中国科学院遗传与发育生物学研究所 | 一种小麦基因组定点改造方法 |
| JP7019233B2 (ja) | 2013-07-11 | 2022-02-15 | モデルナティエックス インコーポレイテッド | ＣＲＩＳＰＲ関連タンパク質をコードする合成ポリヌクレオチドおよび合成ｓｇＲＮＡを含む組成物ならびに使用方法 |
| US10563225B2 (en) | 2013-07-26 | 2020-02-18 | President And Fellows Of Harvard College | Genome engineering |
| CN103388006B (zh) | 2013-07-26 | 2015-10-28 | 华东师范大学 | 一种基因定点突变的构建方法 |
| SG11201601313TA (en) | 2013-08-29 | 2016-03-30 | Univ Temple | Methods and compositions for rna-guided treatment of hiv infection |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| WO2015048690A1 (en) * | 2013-09-27 | 2015-04-02 | The Regents Of The University Of California | Optimized small guide rnas and methods of use |
| WO2015048577A2 (en) | 2013-09-27 | 2015-04-02 | Editas Medicine, Inc. | Crispr-related methods and compositions |
| WO2015065964A1 (en) * | 2013-10-28 | 2015-05-07 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof |
| JP2016536021A (ja) | 2013-11-07 | 2016-11-24 | エディタス・メディシン，インコーポレイテッド | ＣＲＩＳＰＲ関連方法および支配ｇＲＮＡのある組成物 |
| EP3071695A2 (en) * | 2013-11-18 | 2016-09-28 | Crispr Therapeutics AG | Crispr-cas system materials and methods |
| CA2932472A1 (en) | 2013-12-12 | 2015-06-18 | Massachusetts Institute Of Technology | Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| JP2017501149A (ja) | 2013-12-12 | 2017-01-12 | ザ・ブロード・インスティテュート・インコーポレイテッド | 粒子送達構成成分を用いた障害及び疾患の標的化のためのｃｒｉｓｐｒ−ｃａｓ系及び組成物の送達、使用及び治療適用 |
| AU2014361834B2 (en) | 2013-12-12 | 2020-10-22 | Massachusetts Institute Of Technology | CRISPR-Cas systems and methods for altering expression of gene products, structural information and inducible modular Cas enzymes |
| CN103668472B (zh) | 2013-12-31 | 2014-12-24 | 北京大学 | 利用CRISPR/Cas9系统构建真核基因敲除文库的方法 |
| US10354746B2 (en) | 2014-01-27 | 2019-07-16 | Georgia Tech Research Corporation | Methods and systems for identifying CRISPR/Cas off-target sites |
| JP6323228B2 (ja) | 2014-07-18 | 2018-05-16 | 富士電機株式会社 | 電力変換装置 |
| US9932566B2 (en) | 2014-08-07 | 2018-04-03 | Agilent Technologies, Inc. | CIS-blocked guide RNA |
| DK3180426T3 (da) | 2014-08-17 | 2020-03-30 | Broad Inst Inc | Genomredigering ved anvendelse af cas9-nickaser |
| AU2016226077B2 (en) | 2015-03-03 | 2021-12-23 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases with altered PAM specificity |
| MX2017016289A (es) | 2015-06-18 | 2018-08-15 | Broad Inst Inc | Mutaciones de la enzima crispr que reducen los efectos fuera del blanco. |
| JP6186470B2 (ja) | 2016-04-20 | 2017-08-23 | パイオニア株式会社 | 音響装置、音量制御方法、音量制御プログラム及び記録媒体 |
-
2016
- 2016-06-17 MX MX2017016289A patent/MX2017016289A/es unknown
- 2016-06-17 CN CN201811302886.XA patent/CN109536474A/zh active Pending
- 2016-06-17 KR KR1020187001739A patent/KR102575342B1/ko active IP Right Grant
- 2016-06-17 CA CA2989830A patent/CA2989830A1/en active Pending
- 2016-06-17 KR KR1020237029777A patent/KR20230132877A/ko active Search and Examination
- 2016-06-17 SG SG10201912329YA patent/SG10201912329YA/en unknown
- 2016-06-17 TW TW112128864A patent/TW202400626A/zh unknown
- 2016-06-17 CN CN201680035804.2A patent/CN108290933A/zh active Pending
- 2016-06-17 IL IL284808A patent/IL284808B/en unknown
- 2016-06-17 WO PCT/US2016/038034 patent/WO2016205613A1/en active Application Filing
- 2016-06-17 EP EP21178220.6A patent/EP3929287A3/en active Pending
- 2016-06-17 RU RU2021120582A patent/RU2021120582A/ru unknown
- 2016-06-17 RU RU2018101710A patent/RU2752834C2/ru active
- 2016-06-17 TW TW105119140A patent/TWI813532B/zh active
- 2016-06-17 EP EP16734795.4A patent/EP3129393B1/en active Active
- 2016-06-17 JP JP2017565296A patent/JP7107683B2/ja active Active
- 2016-06-17 AU AU2016280893A patent/AU2016280893B2/en active Active
- 2016-06-17 IL IL293323A patent/IL293323B2/en unknown
-
2017
- 2017-12-14 ZA ZA2017/08498A patent/ZA201708498B/en unknown
- 2017-12-14 MX MX2022005304A patent/MX2022005304A/es unknown
- 2017-12-16 US US15/844,528 patent/US10876100B2/en active Active
- 2017-12-17 IL IL256368A patent/IL256368B/en unknown
-
2018
- 2018-10-11 JP JP2018192321A patent/JP6793699B2/ja active Active
- 2018-10-11 US US16/158,295 patent/US10494621B2/en active Active
-
2022
- 2022-02-21 AU AU2022201165A patent/AU2022201165A1/en active Pending
- 2022-07-13 JP JP2022112170A patent/JP2022141778A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2021120582A (ru) | Мутации фермента crispr, уменьшающие нецелевые эффекты | |
| Guo et al. | Cryo-EM structures reveal mechanism and inhibition of DNA targeting by a CRISPR-Cas surveillance complex | |
| US20240200044A1 (en) | Evolution of talens | |
| EA201991440A1 (ru) | ТЕРМОСТАБИЛЬНЫЕ НУКЛЕАЗЫ Cas9 | |
| IL309801B1 (en) | Use of protein domains interacting with the nucleosome to enhance targeted genome modification | |
| JP2023002785A (ja) | 変異ｃａｓ９タンパク質 | |
| WO2007115578A8 (en) | Synthetic mecp2 sequence for protein substitution therapy | |
| JP2020532967A (ja) | 変更されたＰＡＭ特異性を有する遺伝子操作されたＣＲＩＳＰＲ−Ｃａｓ９ヌクレアーゼ | |
| JP2017513479A5 (ru) | ||
| WO2010132092A3 (en) | Cytidine deaminase fusions and related methods | |
| MY175477A (en) | Variant aav and compositions, methods and uses for gene transfer to cells, organs and tissues | |
| SA522433360B1 (ar) | L-أَسْباراجيناز مُعدل | |
| JP2018528237A5 (ru) | ||
| WO2015089486A3 (en) | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems | |
| You et al. | Mechanistic investigations of the dehydration reaction of lacticin 481 synthetase using site-directed mutagenesis | |
| RU2022103641A (ru) | Искусственная модификация генома для регуляции экспрессии гена | |
| JP2024502630A (ja) | コンテキスト依存性二本鎖ｄｎａ特異的デアミナーゼ及びその使用 | |
| Merrill et al. | High pressure liquid chromatography purification of UP1 and UP2, two related single-stranded nucleic acid-binding proteins from calf thymus. | |
| WO2020049158A1 (en) | Compositions and methods for improved nucleases | |
| Sarre et al. | Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans | |
| WO2013136175A3 (en) | Repeat variable diresidues for targeting nucleotides | |
| Wittmann et al. | Genomic and molecular analysis of phage CMP1 from Clavibacter michiganensis subspecies michiganensis | |
| Sood et al. | Highly specific culture-independent detection of YGNGV motif-containing pediocin-producing strains | |
| Frumerie et al. | Cooperative interactions between bacteriophage P2 integrase and its accessory factors IHF and Cox | |
| Huang et al. | The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein |