ES2774677T3 - Proteínas CAS9 mutantes - Google Patents
Proteínas CAS9 mutantes Download PDFInfo
- Publication number
- ES2774677T3 ES2774677T3 ES14864613T ES14864613T ES2774677T3 ES 2774677 T3 ES2774677 T3 ES 2774677T3 ES 14864613 T ES14864613 T ES 14864613T ES 14864613 T ES14864613 T ES 14864613T ES 2774677 T3 ES2774677 T3 ES 2774677T3
- Authority
- ES
- Spain
- Prior art keywords
- cas9
- amino acid
- conservation
- nucleic acid
- acid sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108091033409 CRISPR Proteins 0.000 title claims abstract description 189
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 48
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 35
- 150000001413 amino acids Chemical class 0.000 claims abstract description 32
- 230000000694 effects Effects 0.000 claims abstract description 30
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 19
- 230000004568 DNA-binding Effects 0.000 claims abstract description 18
- 238000002864 sequence alignment Methods 0.000 claims abstract 2
- 101710163270 Nuclease Proteins 0.000 claims description 39
- 108090000623 proteins and genes Proteins 0.000 claims description 36
- 102000039446 nucleic acids Human genes 0.000 claims description 27
- 108020004707 nucleic acids Proteins 0.000 claims description 27
- 102000004169 proteins and genes Human genes 0.000 claims description 22
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 7
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 46
- 241000194020 Streptococcus thermophilus Species 0.000 description 43
- 210000004027 cell Anatomy 0.000 description 39
- 108020004414 DNA Proteins 0.000 description 36
- 238000012217 deletion Methods 0.000 description 36
- 230000037430 deletion Effects 0.000 description 36
- 101710096438 DNA-binding protein Proteins 0.000 description 33
- 238000010354 CRISPR gene editing Methods 0.000 description 18
- 239000013612 plasmid Substances 0.000 description 18
- 238000003556 assay Methods 0.000 description 17
- 241000588724 Escherichia coli Species 0.000 description 16
- 108020005004 Guide RNA Proteins 0.000 description 14
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 102100035102 E3 ubiquitin-protein ligase MYCBP2 Human genes 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 210000004899 c-terminal region Anatomy 0.000 description 10
- 239000012636 effector Substances 0.000 description 9
- 230000002103 transcriptional effect Effects 0.000 description 9
- 241000894007 species Species 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 238000013459 approach Methods 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000013461 design Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 5
- 241000589602 Francisella tularensis Species 0.000 description 5
- 241000588650 Neisseria meningitidis Species 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 229940118764 francisella tularensis Drugs 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 125000006850 spacer group Chemical group 0.000 description 5
- 230000037426 transcriptional repression Effects 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000003708 edge detection Methods 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 238000002887 multiple sequence alignment Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 108700028369 Alleles Proteins 0.000 description 3
- 241000203069 Archaea Species 0.000 description 3
- 108091079001 CRISPR RNA Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 241000193996 Streptococcus pyogenes Species 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 101150063416 add gene Proteins 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000008045 co-localization Effects 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 239000013607 AAV vector Substances 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- 108091032955 Bacterial small RNA Proteins 0.000 description 2
- 241000589875 Campylobacter jejuni Species 0.000 description 2
- 241000193155 Clostridium botulinum Species 0.000 description 2
- 241001485655 Corynebacterium glutamicum ATCC 13032 Species 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 241000423296 Gluconacetobacter diazotrophicus PA1 5 Species 0.000 description 2
- 102100025169 Max-binding protein MNT Human genes 0.000 description 2
- 108020005196 Mitochondrial DNA Proteins 0.000 description 2
- 241000156211 Neisseria meningitidis 053442 Species 0.000 description 2
- 241000529650 Neisseria meningitidis Z2491 Species 0.000 description 2
- 241000554781 Neisseria meningitidis alpha14 Species 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 108020005202 Viral DNA Proteins 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 108091005763 multidomain proteins Proteins 0.000 description 2
- 238000007857 nested PCR Methods 0.000 description 2
- 210000001778 pluripotent stem cell Anatomy 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 108091006107 transcriptional repressors Proteins 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- 241001041760 Acidothermus cellulolyticus 11B Species 0.000 description 1
- 241000417230 Actinobacillus succinogenes 130Z Species 0.000 description 1
- 241000778935 Akkermansia muciniphila ATCC BAA-835 Species 0.000 description 1
- 241000589941 Azospirillum Species 0.000 description 1
- 241000257169 Bacillus cereus ATCC 10987 Species 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 241000586987 Bifidobacterium dentium Bd1 Species 0.000 description 1
- 241001209261 Bifidobacterium longum DJO10A Species 0.000 description 1
- 241000589173 Bradyrhizobium Species 0.000 description 1
- 241001453247 Campylobacter jejuni subsp. doylei Species 0.000 description 1
- 241000941427 Campylobacter lari RM2100 Species 0.000 description 1
- 241001034636 Capnocytophaga ochracea DSM 7271 Species 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 241001509423 Clostridium botulinum B Species 0.000 description 1
- 241001509504 Clostridium botulinum F Species 0.000 description 1
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 1
- 241001487058 Corynebacterium efficiens YS-314 Species 0.000 description 1
- 241000671338 Corynebacterium glutamicum R Species 0.000 description 1
- 241001525611 Corynebacterium kroppenstedtii DSM 44385 Species 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 241001082278 Desulfovibrio salexigens DSM 2638 Species 0.000 description 1
- 241000688137 Diaphorobacter Species 0.000 description 1
- 241000933091 Dinoroseobacter shibae DFL 12 = DSM 16493 Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000448576 Elusimicrobium minutum Pei191 Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001333951 Escherichia coli O157 Species 0.000 description 1
- 241000186394 Eubacterium Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000608038 Fibrobacter succinogenes subsp. succinogenes S85 Species 0.000 description 1
- 241000359186 Finegoldia magna ATCC 29328 Species 0.000 description 1
- 241000382842 Flavobacterium psychrophilum Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001453258 Helicobacter hepaticus Species 0.000 description 1
- 108010015268 Integration Host Factors Proteins 0.000 description 1
- 241000256602 Isoptera Species 0.000 description 1
- 241001596092 Kribbella flavida DSM 17836 Species 0.000 description 1
- 244000199866 Lactobacillus casei Species 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 241000917009 Lactobacillus rhamnosus GG Species 0.000 description 1
- 241001427851 Lactobacillus salivarius UCC118 Species 0.000 description 1
- 241001193656 Legionella pneumophila str. Paris Species 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 241000186805 Listeria innocua Species 0.000 description 1
- 241001378931 Methanococcus maripaludis C7 Species 0.000 description 1
- 108010086093 Mung Bean Nuclease Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 241000825684 Mycobacterium abscessus ATCC 19977 Species 0.000 description 1
- 241000204022 Mycoplasma gallisepticum Species 0.000 description 1
- 241000107400 Mycoplasma mobile 163K Species 0.000 description 1
- 241001135743 Mycoplasma penetrans Species 0.000 description 1
- 241000051161 Mycoplasma synoviae 53 Species 0.000 description 1
- 241001648684 Nitrobacter hamburgensis X14 Species 0.000 description 1
- 241001037736 Nocardia farcinica IFM 10152 Species 0.000 description 1
- 241000601272 Parvibaculum lavamentivorans DS-1 Species 0.000 description 1
- 241000606856 Pasteurella multocida Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000981393 Persephonella marina Species 0.000 description 1
- 102220481901 Probable rRNA-processing protein EBP2_D13A_mutation Human genes 0.000 description 1
- 241000773205 Pseudarthrobacter chlorophenolicus A6 Species 0.000 description 1
- 241000695265 Pseudoalteromonas atlantica T6c Species 0.000 description 1
- 241000712909 Reticuloendotheliosis virus Species 0.000 description 1
- 241000647111 Rhodococcus erythropolis PR4 Species 0.000 description 1
- 241001459443 Rhodococcus jostii RHA1 Species 0.000 description 1
- 241001113889 Rhodococcus opacus B4 Species 0.000 description 1
- 241001303434 Rhodopseudomonas palustris BisB18 Species 0.000 description 1
- 241001303431 Rhodopseudomonas palustris BisB5 Species 0.000 description 1
- 241000134686 Rhodospirillum rubrum ATCC 11170 Species 0.000 description 1
- 102000003661 Ribonuclease III Human genes 0.000 description 1
- 108010057163 Ribonuclease III Proteins 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 241000516659 Roseiflexus Species 0.000 description 1
- 241000504328 Roseiflexus castenholzii DSM 13941 Species 0.000 description 1
- 241000933177 Shewanella pealeana ATCC 700345 Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241001496704 Slackia heliotrinireducens DSM 20476 Species 0.000 description 1
- 241000713896 Spleen necrosis virus Species 0.000 description 1
- 241000756832 Streptobacillus moniliformis DSM 12112 Species 0.000 description 1
- 241000193985 Streptococcus agalactiae Species 0.000 description 1
- 241001209210 Streptococcus agalactiae A909 Species 0.000 description 1
- 241001540742 Streptococcus agalactiae NEM316 Species 0.000 description 1
- 241000194042 Streptococcus dysgalactiae Species 0.000 description 1
- 241000120569 Streptococcus equi subsp. zooepidemicus Species 0.000 description 1
- 241001167808 Streptococcus gallolyticus UCN34 Species 0.000 description 1
- 241001147754 Streptococcus gordonii str. Challis Species 0.000 description 1
- 241000194019 Streptococcus mutans Species 0.000 description 1
- 241000672607 Streptococcus mutans NN2025 Species 0.000 description 1
- 241000320123 Streptococcus pyogenes M1 GAS Species 0.000 description 1
- 241000103155 Streptococcus pyogenes MGAS10270 Species 0.000 description 1
- 241000103160 Streptococcus pyogenes MGAS10750 Species 0.000 description 1
- 241000103154 Streptococcus pyogenes MGAS2096 Species 0.000 description 1
- 241001520169 Streptococcus pyogenes MGAS315 Species 0.000 description 1
- 241001148739 Streptococcus pyogenes MGAS5005 Species 0.000 description 1
- 241001332083 Streptococcus pyogenes MGAS6180 Species 0.000 description 1
- 241000103156 Streptococcus pyogenes MGAS9429 Species 0.000 description 1
- 241001496716 Streptococcus pyogenes NZ131 Species 0.000 description 1
- 241001455236 Streptococcus pyogenes SSI-1 Species 0.000 description 1
- 101100166147 Streptococcus thermophilus cas9 gene Proteins 0.000 description 1
- 241000192593 Synechocystis sp. PCC 6803 Species 0.000 description 1
- 241001496699 Thermomonospora curvata DSM 43183 Species 0.000 description 1
- 241000322994 Tolumonas auensis DSM 9187 Species 0.000 description 1
- 241000589892 Treponema denticola Species 0.000 description 1
- 241000999858 Treponema denticola ATCC 35405 Species 0.000 description 1
- 241000847071 Verminephrobacter eiseniae EF01-2 Species 0.000 description 1
- 241000605939 Wolinella succinogenes Species 0.000 description 1
- 241000883281 [Clostridium] cellulolyticum H10 Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000007845 assembly PCR Methods 0.000 description 1
- 230000007940 bacterial gene expression Effects 0.000 description 1
- 230000008970 bacterial immunity Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 229940059406 lactobacillus rhamnosus gg Drugs 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000012536 packaging technology Methods 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- -1 repressors Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 102200097286 rs199472825 Human genes 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229940115920 streptococcus dysgalactiae Drugs 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- 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)
-
- 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
- C12Q1/6897—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
-
- 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
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- 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
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/916—Hydrolases (3) acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
- G01N2333/922—Ribonucleases (RNAses); Deoxyribonucleases (DNAses)
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361906374P | 2013-11-19 | 2013-11-19 | |
| PCT/US2014/066375 WO2015077318A1 (en) | 2013-11-19 | 2014-11-19 | Mutant cas9 proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2774677T3 true ES2774677T3 (es) | 2020-07-22 |
Family
ID=53180093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14864613T Active ES2774677T3 (es) | 2013-11-19 | 2014-11-19 | Proteínas CAS9 mutantes |
Country Status (8)
| Country | Link |
|---|---|
| US (5) | US9074199B1 (https=) |
| EP (2) | EP3071694B1 (https=) |
| JP (4) | JP6984096B2 (https=) |
| KR (1) | KR102212295B1 (https=) |
| AU (2) | AU2014353128B2 (https=) |
| CA (2) | CA2930829C (https=) |
| ES (1) | ES2774677T3 (https=) |
| WO (1) | WO2015077318A1 (https=) |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10323236B2 (en) | 2011-07-22 | 2019-06-18 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| US10760064B2 (en) | 2013-03-15 | 2020-09-01 | The General Hospital Corporation | RNA-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci |
| CN112301024A (zh) | 2013-03-15 | 2021-02-02 | 通用医疗公司 | 使用RNA引导的FokI核酸酶(RFN)提高RNA引导的基因组编辑的特异性 |
| WO2014204578A1 (en) | 2013-06-21 | 2014-12-24 | The General Hospital Corporation | Using rna-guided foki nucleases (rfns) to increase specificity for rna-guided genome editing |
| EP3004339B1 (en) * | 2013-05-29 | 2021-07-07 | Cellectis | New compact scaffold of cas9 in the type ii crispr system |
| US9163284B2 (en) | 2013-08-09 | 2015-10-20 | 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 |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| CN106459995B (zh) | 2013-11-07 | 2020-02-21 | 爱迪塔斯医药有限公司 | 使用统治型gRNA的CRISPR相关方法和组合物 |
| US9074199B1 (en) * | 2013-11-19 | 2015-07-07 | President And Fellows Of Harvard College | Mutant Cas9 proteins |
| US20150165054A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting caspase-9 point mutations |
| EP3690044B1 (en) | 2014-02-11 | 2024-01-10 | The Regents of the University of Colorado, a body corporate | Crispr enabled multiplexed genome engineering |
| US11028388B2 (en) | 2014-03-05 | 2021-06-08 | Editas Medicine, Inc. | CRISPR/Cas-related methods and compositions for treating Usher syndrome and retinitis pigmentosa |
| US11141493B2 (en) | 2014-03-10 | 2021-10-12 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
| ES2745769T3 (es) | 2014-03-10 | 2020-03-03 | Editas Medicine Inc | Procedimientos y composiciones relacionados con CRISPR/CAS para tratar la amaurosis congénita de Leber 10 (LCA10) |
| US11339437B2 (en) | 2014-03-10 | 2022-05-24 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
| EP3122880B1 (en) | 2014-03-26 | 2021-05-05 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating sickle cell disease |
| EP3540061A1 (en) | 2014-04-02 | 2019-09-18 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating primary open angle glaucoma |
| US10077453B2 (en) | 2014-07-30 | 2018-09-18 | President And Fellows Of Harvard College | CAS9 proteins including ligand-dependent inteins |
| AU2015330699B2 (en) | 2014-10-10 | 2021-12-02 | Editas Medicine, Inc. | Compositions and methods for promoting homology directed repair |
| US10612042B2 (en) | 2014-10-24 | 2020-04-07 | Avectas Limited | Delivery across cell plasma membranes |
| EP4464338A3 (en) | 2014-11-07 | 2025-02-12 | Editas Medicine, Inc. | Systems for improving crispr/cas-mediated genome-editing |
| CA2969619A1 (en) | 2014-12-03 | 2016-06-09 | Agilent Technologies, Inc. | Guide rna with chemical modifications |
| KR102888521B1 (ko) | 2015-04-06 | 2025-11-19 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | Crispr/cas-매개 유전자 조절을 위한 화학적으로 변형된 가이드 rna |
| JP2018522249A (ja) | 2015-04-24 | 2018-08-09 | エディタス・メディシン、インコーポレイテッド | Ｃａｓ９分子／ガイドｒｎａ分子複合体の評価 |
| CA2986310A1 (en) | 2015-05-11 | 2016-11-17 | Editas Medicine, Inc. | Optimized crispr/cas9 systems and methods for gene editing in stem cells |
| CN108025188A (zh) | 2015-06-01 | 2018-05-11 | 天普大学-联邦高等教育系统 | 用于hiv感染的rna导向治疗的方法和组合物 |
| WO2016196655A1 (en) | 2015-06-03 | 2016-12-08 | The Regents Of The University Of California | Cas9 variants and methods of use thereof |
| CN108026526B (zh) | 2015-06-09 | 2023-05-12 | 爱迪塔斯医药公司 | 用于改善移植的crispr/cas相关方法和组合物 |
| WO2017004261A1 (en) | 2015-06-29 | 2017-01-05 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
| US9512446B1 (en) | 2015-08-28 | 2016-12-06 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| US9926546B2 (en) | 2015-08-28 | 2018-03-27 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| EP3353296B1 (en) | 2015-09-24 | 2020-11-04 | Editas Medicine, Inc. | Use of exonucleases to improve crispr/cas-mediated genome editing |
| IL310721B2 (en) | 2015-10-23 | 2025-11-01 | Harvard College | Nucleobase editors and uses thereof |
| CA3005968A1 (en) | 2015-11-23 | 2017-06-01 | The Regents Of The University Of California | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 |
| CA3009715A1 (en) | 2015-12-30 | 2017-07-06 | Avectas Limited | Vector-free delivery of gene editing proteins and compositions to cells and tissues |
| WO2017118720A1 (en) * | 2016-01-08 | 2017-07-13 | Novozymes A/S | Genome editing in bacillus host cells |
| US11512311B2 (en) | 2016-03-25 | 2022-11-29 | Editas Medicine, Inc. | Systems and methods for treating alpha 1-antitrypsin (A1AT) deficiency |
| US11597924B2 (en) | 2016-03-25 | 2023-03-07 | Editas Medicine, Inc. | Genome editing systems comprising repair-modulating enzyme molecules and methods of their use |
| GB2565461B (en) * | 2016-03-31 | 2022-04-13 | Harvard College | Methods and compositions for the single tube preparation of sequencing libraries using Cas9 |
| US11236313B2 (en) | 2016-04-13 | 2022-02-01 | Editas Medicine, Inc. | Cas9 fusion molecules, gene editing systems, and methods of use thereof |
| US10767175B2 (en) | 2016-06-08 | 2020-09-08 | Agilent Technologies, Inc. | High specificity genome editing using chemically modified guide RNAs |
| AU2017280353B2 (en) | 2016-06-24 | 2021-11-11 | Inscripta, Inc. | Methods for generating barcoded combinatorial libraries |
| BR112019001887A2 (pt) | 2016-08-02 | 2019-07-09 | Editas Medicine Inc | composições e métodos para o tratamento de doença associada a cep290 |
| CN110214183A (zh) | 2016-08-03 | 2019-09-06 | 哈佛大学的校长及成员们 | 腺苷核碱基编辑器及其用途 |
| WO2018031683A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| US20190225974A1 (en) | 2016-09-23 | 2019-07-25 | BASF Agricultural Solutions Seed US LLC | Targeted genome optimization in plants |
| KR102622411B1 (ko) | 2016-10-14 | 2024-01-10 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵염기 에디터의 aav 전달 |
| SG10201913505WA (en) | 2016-10-17 | 2020-02-27 | Univ Nanyang Tech | Truncated crispr-cas proteins for dna targeting |
| EP4520828A3 (en) | 2016-11-15 | 2025-07-09 | The Schepens Eye Research Institute, Inc. | Compositions and methods for the treatment of aberrant angiogenesis |
| EP3555297A1 (en) | 2016-12-19 | 2019-10-23 | Editas Medicine, Inc. | Assessing nuclease cleavage |
| WO2018115973A2 (en) | 2016-12-22 | 2018-06-28 | Avectas Limited | Vector-free intracellular delivery by reversible permeabilisation |
| WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
| JP7229923B2 (ja) | 2017-01-06 | 2023-02-28 | エディタス・メディシン、インコーポレイテッド | ヌクレアーゼ切断を評価する方法 |
| US11730828B2 (en) | 2017-02-07 | 2023-08-22 | The Regents Of The University Of California | Gene therapy for haploinsufficiency |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| US12390514B2 (en) | 2017-03-09 | 2025-08-19 | President And Fellows Of Harvard College | Cancer vaccine |
| US11542496B2 (en) | 2017-03-10 | 2023-01-03 | President And Fellows Of Harvard College | Cytosine to guanine base editor |
| WO2018170184A1 (en) | 2017-03-14 | 2018-09-20 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
| US11499151B2 (en) | 2017-04-28 | 2022-11-15 | Editas Medicine, Inc. | Methods and systems for analyzing guide RNA molecules |
| WO2018208998A1 (en) | 2017-05-10 | 2018-11-15 | The Regents Of The University Of California | Directed editing of cellular rna via nuclear delivery of crispr/cas9 |
| EP3622070A2 (en) | 2017-05-10 | 2020-03-18 | Editas Medicine, Inc. | Crispr/rna-guided nuclease systems and methods |
| US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
| MX2019014640A (es) | 2017-06-09 | 2020-10-05 | Editas Medicine Inc | Nucleasas de repeticiones palíndromicas agrupadas y regularmente interespaciadas de proteina asociada 9 (cas9) genomanipuladas. |
| MX2019014578A (es) | 2017-06-21 | 2020-12-01 | Timothy A Bertram | Celulas renales bioactivas inmunoprivilegiadas para el tratamiento de enfermedad renal. |
| 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 |
| 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 |
| CN111801345A (zh) | 2017-07-28 | 2020-10-20 | 哈佛大学的校长及成员们 | 使用噬菌体辅助连续进化(pace)的进化碱基编辑器的方法和组合物 |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| AU2018338318B2 (en) | 2017-09-21 | 2022-12-22 | Massachusetts Institute Of Technology | Systems, methods, and compositions for targeted nucleic acid editing |
| KR20250107288A (ko) | 2017-10-16 | 2025-07-11 | 더 브로드 인스티튜트, 인코퍼레이티드 | 아데노신 염기 편집제의 용도 |
| US11739326B2 (en) | 2017-11-14 | 2023-08-29 | Massachusetts Eye And Ear Infirmary | RUNX1 inhibition for treatment of proliferative vitreoretinopathy and conditions associated with epithelial to mesenchymal transition |
| US12406749B2 (en) | 2017-12-15 | 2025-09-02 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| AU2019207409B2 (en) | 2018-01-12 | 2023-02-23 | Basf Se | Gene underlying the number of spikelets per spike qtl in wheat on chromosome 7a |
| WO2019147743A1 (en) | 2018-01-26 | 2019-08-01 | Massachusetts Institute Of Technology | Structure-guided chemical modification of guide rna and its applications |
| KR102465067B1 (ko) * | 2018-02-15 | 2022-11-10 | 시그마-알드리치 컴퍼니., 엘엘씨 | 진핵 게놈 변형을 위한 조작된 cas9 시스템 |
| KR102907245B1 (ko) | 2018-03-14 | 2026-01-05 | 에디타스 메디신, 인코포레이티드 | 혈색소병증 치료를 위한 시스템 및 방법 |
| MA52074A (fr) * | 2018-03-19 | 2021-01-27 | Bayer Healthcare Llc | Nouveaux systèmes d'endonucléase à arn programmable et leurs utilisations |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| EP3802779A1 (en) | 2018-06-01 | 2021-04-14 | Avectas Limited | Cell engineering platform |
| EP3823633A4 (en) | 2018-06-29 | 2023-05-03 | Editas Medicine, Inc. | SYNTHETIC LEAD MOLECULES, COMPOSITIONS AND METHODS RELATED THERETO |
| US12522807B2 (en) | 2018-07-09 | 2026-01-13 | The Broad Institute, Inc. | RNA programmable epigenetic RNA modifiers and uses thereof |
| WO2020076976A1 (en) | 2018-10-10 | 2020-04-16 | Readcoor, Inc. | Three-dimensional spatial molecular indexing |
| CN113166738A (zh) * | 2018-10-24 | 2021-07-23 | 摩大力斯医疗株式会社 | 经改造的Cas9蛋白及其用途 |
| WO2020092453A1 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Nucleobase editors comprising geocas9 and uses thereof |
| CN113710799B (zh) | 2018-11-28 | 2024-11-12 | 克里斯珀医疗股份公司 | 用于在LNP中使用的编码CAS9的优化mRNA |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| WO2020191233A1 (en) | 2019-03-19 | 2020-09-24 | The Broad Institute, Inc. | Methods and compositions for editing nucleotide sequences |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| CN110241099B (zh) * | 2019-06-05 | 2021-04-30 | 复旦大学 | 酿脓链球菌的CRISPR核酸酶SpCas9 的截短变异体及其应用 |
| CN114269912A (zh) * | 2019-06-14 | 2022-04-01 | 阿伯生物技术公司 | 新型crispr dna靶向酶及系统 |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| US11060141B1 (en) | 2019-12-23 | 2021-07-13 | Stilla Technologies | Multiplex drop-off digital polymerase chain reaction methods |
| US20210290757A1 (en) | 2020-03-23 | 2021-09-23 | Avectas Limited | Engineering of dendritic cells for generation of vaccines against sars-cov-2 |
| IL297761A (en) | 2020-05-08 | 2022-12-01 | Broad Inst Inc | Methods and compositions for simultaneously editing two helices of a designated double-helix nucleotide sequence |
| AU2022213019A1 (en) | 2021-02-01 | 2023-08-10 | Avectas Limited | Delivery platform |
| WO2022225978A1 (en) | 2021-04-21 | 2022-10-27 | The Regents Of The University Of California | Use of a split dcas fusion protein system for epigenetic editing |
| JP2024534945A (ja) | 2021-09-10 | 2024-09-26 | アジレント・テクノロジーズ・インク | 化学修飾を有するプライム編集のためのガイドｒｎａ |
| WO2023064813A2 (en) * | 2021-10-13 | 2023-04-20 | University Of Massachusetts | Modified guide rnas for neisseria meningitidis cas9 |
| EP4426828A1 (en) | 2021-11-01 | 2024-09-11 | Tome Biosciences, Inc. | Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo |
| 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 |
| 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 |
| WO2024234006A1 (en) | 2023-05-11 | 2024-11-14 | Tome Biosciences, Inc. | Systems, compositions, and methods for targeting liver sinusodial endothelial cells (lsecs) |
| WO2025050069A1 (en) | 2023-09-01 | 2025-03-06 | Tome Biosciences, Inc. | Programmable gene insertion using engineered integration enzymes |
| WO2025078978A1 (en) | 2023-10-09 | 2025-04-17 | Avectas Limited | Transfection of cells via reversible permeabilization |
| WO2025149983A2 (en) | 2024-01-12 | 2025-07-17 | Avectas Limited | Delivery platform with integrated non-viral transfection and cell processing |
| WO2025149984A2 (en) | 2024-01-12 | 2025-07-17 | Avectas Limited | Delivery platform with flow-through system (fts) |
| EP4677108A1 (en) | 2024-04-22 | 2026-01-14 | Basecamp Research Ltd | Method and compositions for detecting off-target editing |
| WO2025224182A2 (en) | 2024-04-23 | 2025-10-30 | Basecamp Research Ltd | Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2431858A1 (en) * | 2000-12-14 | 2002-06-20 | Genencor International, Inc. | Targeted enzymes comprising substrate recognition sites and target binding sites |
| CN101688241B (zh) | 2007-03-02 | 2015-01-21 | 杜邦营养生物科学有限公司 | 具有改善的噬菌体抗性的培养物 |
| KR100952754B1 (ko) | 2007-09-28 | 2010-04-14 | 동아대학교 산학협력단 | 토양 메타게놈에서 유래한 항생 활성을 암호화하는유전자군 |
| 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 |
| US10087431B2 (en) | 2010-03-10 | 2018-10-02 | The Regents Of The University Of California | Methods of generating nucleic acid fragments |
| MX2012013037A (es) | 2010-05-10 | 2013-07-29 | Univ California | Composiciones de endorribonucleasa y metodos de uso de las mismas. |
| US9089520B2 (en) | 2010-05-21 | 2015-07-28 | Baylor College Of Medicine | Methods for inducing selective apoptosis |
| WO2012164565A1 (en) | 2011-06-01 | 2012-12-06 | Yeda Research And Development Co. Ltd. | Compositions and methods for downregulating prokaryotic genes |
| GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
| US20150166969A1 (en) | 2012-02-24 | 2015-06-18 | Fred Hutchinson Cancer Research Center | Compositions and methods for the treatment of hemoglobinopathies |
| WO2013130824A1 (en) | 2012-02-29 | 2013-09-06 | Sangamo Biosciences, Inc. | Methods and compositions for treating huntington's disease |
| 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 |
| AU2013259647B2 (en) * | 2012-05-07 | 2018-11-08 | Corteva Agriscience Llc | Methods and compositions for nuclease-mediated targeted integration of transgenes |
| AU2013266968B2 (en) | 2012-05-25 | 2017-06-29 | Emmanuelle CHARPENTIER | Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription |
| WO2014022702A2 (en) | 2012-08-03 | 2014-02-06 | The Regents Of The University Of California | Methods and compositions for controlling gene expression by rna processing |
| CN113355357B (zh) | 2012-12-12 | 2024-12-03 | 布罗德研究所有限公司 | 对用于序列操纵的改进的系统、方法和酶组合物进行的工程化和优化 |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| RU2662932C2 (ru) * | 2013-03-14 | 2018-07-31 | Карибо Биосайенсиз, Инк. | Композиции и способы с участием нуклеиновых кислот, нацеленных на нуклеиновые кислоты |
| US9234213B2 (en) * | 2013-03-15 | 2016-01-12 | System Biosciences, Llc | Compositions and methods directed to CRISPR/Cas genomic engineering systems |
| US9074199B1 (en) * | 2013-11-19 | 2015-07-07 | President And Fellows Of Harvard College | Mutant Cas9 proteins |
-
2014
- 2014-06-30 US US14/319,784 patent/US9074199B1/en active Active
- 2014-11-19 KR KR1020167015908A patent/KR102212295B1/ko active Active
- 2014-11-19 EP EP14864613.6A patent/EP3071694B1/en active Active
- 2014-11-19 CA CA2930829A patent/CA2930829C/en active Active
- 2014-11-19 JP JP2016532542A patent/JP6984096B2/ja active Active
- 2014-11-19 ES ES14864613T patent/ES2774677T3/es active Active
- 2014-11-19 US US15/037,696 patent/US10100291B2/en active Active
- 2014-11-19 AU AU2014353128A patent/AU2014353128B2/en active Active
- 2014-11-19 EP EP19213645.5A patent/EP3647418A1/en active Pending
- 2014-11-19 CA CA3191825A patent/CA3191825A1/en active Pending
- 2014-11-19 WO PCT/US2014/066375 patent/WO2015077318A1/en not_active Ceased
-
2018
- 2018-10-11 US US16/157,481 patent/US10435679B2/en active Active
-
2019
- 2019-04-16 JP JP2019077510A patent/JP7020635B2/ja active Active
- 2019-06-13 US US16/440,241 patent/US10683490B2/en active Active
-
2020
- 2020-04-20 US US16/852,592 patent/US11286470B2/en active Active
- 2020-07-23 AU AU2020207837A patent/AU2020207837B2/en active Active
- 2020-12-15 JP JP2020207668A patent/JP7631778B2/ja active Active
-
2022
- 2022-10-28 JP JP2022173487A patent/JP7469433B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US11286470B2 (en) | 2022-03-29 |
| AU2014353128A1 (en) | 2016-06-09 |
| US20190040371A1 (en) | 2019-02-07 |
| CA3191825A1 (en) | 2015-05-28 |
| US10100291B2 (en) | 2018-10-16 |
| US20190367892A1 (en) | 2019-12-05 |
| JP2017501688A (ja) | 2017-01-19 |
| JP2023002785A (ja) | 2023-01-10 |
| EP3071694A4 (en) | 2017-10-25 |
| JP2019150033A (ja) | 2019-09-12 |
| KR102212295B1 (ko) | 2021-02-03 |
| CA2930829A1 (en) | 2015-05-28 |
| JP7469433B2 (ja) | 2024-04-16 |
| AU2020207837B2 (en) | 2023-04-06 |
| CA2930829C (en) | 2023-05-02 |
| JP7020635B2 (ja) | 2022-02-16 |
| US20160298097A1 (en) | 2016-10-13 |
| JP6984096B2 (ja) | 2021-12-17 |
| US10435679B2 (en) | 2019-10-08 |
| JP7631778B2 (ja) | 2025-02-19 |
| US9074199B1 (en) | 2015-07-07 |
| EP3071694B1 (en) | 2020-01-08 |
| JP2021052784A (ja) | 2021-04-08 |
| EP3647418A1 (en) | 2020-05-06 |
| US20200283747A1 (en) | 2020-09-10 |
| EP3071694A1 (en) | 2016-09-28 |
| AU2020207837A1 (en) | 2020-08-13 |
| US10683490B2 (en) | 2020-06-16 |
| AU2014353128B2 (en) | 2020-04-30 |
| WO2015077318A1 (en) | 2015-05-28 |
| KR20160079119A (ko) | 2016-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2774677T3 (es) | Proteínas CAS9 mutantes | |
| RU2771583C1 (ru) | Ортогональные белки cas9 для рнк-направляемой регуляции и редактирования генов | |
| KR102884236B1 (ko) | Rna-가이드된 전사 조절 | |
| US20200291370A1 (en) | Mutant Cas Proteins | |
| WO2017136520A1 (en) | Mitochondrial genome editing and regulation |