BR112016000571B1 - Métodos in vitro para modular a expressão e para alterar um ou mais ácidos nucleicos alvo em uma célula simultaneamente com a regulação da expressão de um ou mais ácidos nucleicos alvo em uma célula, bem como célula de levedura ou bactéria compreendendo ácidos nucleicos - Google Patents
Métodos in vitro para modular a expressão e para alterar um ou mais ácidos nucleicos alvo em uma célula simultaneamente com a regulação da expressão de um ou mais ácidos nucleicos alvo em uma célula, bem como célula de levedura ou bactéria compreendendo ácidos nucleicos Download PDFInfo
- Publication number
- BR112016000571B1 BR112016000571B1 BR112016000571-6A BR112016000571A BR112016000571B1 BR 112016000571 B1 BR112016000571 B1 BR 112016000571B1 BR 112016000571 A BR112016000571 A BR 112016000571A BR 112016000571 B1 BR112016000571 B1 BR 112016000571B1
- Authority
- BR
- Brazil
- Prior art keywords
- protein
- rna
- nucleic acid
- target nucleic
- fact
- Prior art date
Links
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 191
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 188
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 188
- 238000000034 method Methods 0.000 title claims abstract description 79
- 230000014509 gene expression Effects 0.000 title claims abstract description 64
- 230000001105 regulatory effect Effects 0.000 title claims description 107
- 230000001580 bacterial effect Effects 0.000 title claims description 23
- 238000000338 in vitro Methods 0.000 title claims description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 title claims 15
- 108091033409 CRISPR Proteins 0.000 claims abstract description 200
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 154
- 210000004027 cell Anatomy 0.000 claims description 157
- 108020004414 DNA Proteins 0.000 claims description 139
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 120
- 102000052510 DNA-Binding Proteins Human genes 0.000 claims description 113
- 102000004169 proteins and genes Human genes 0.000 claims description 112
- 108020005004 Guide RNA Proteins 0.000 claims description 103
- 230000002103 transcriptional effect Effects 0.000 claims description 96
- 101710163270 Nuclease Proteins 0.000 claims description 81
- 101710096438 DNA-binding protein Proteins 0.000 claims description 80
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 74
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 44
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 44
- 108700020911 DNA-Binding Proteins Proteins 0.000 claims description 33
- 238000010354 CRISPR gene editing Methods 0.000 claims description 28
- 230000000295 complement effect Effects 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 239000002773 nucleotide Substances 0.000 claims description 21
- 125000003729 nucleotide group Chemical group 0.000 claims description 21
- 230000004927 fusion Effects 0.000 claims description 20
- 230000008045 co-localization Effects 0.000 claims description 18
- 230000004570 RNA-binding Effects 0.000 claims description 13
- 108091006106 transcriptional activators Proteins 0.000 claims description 13
- 230000004568 DNA-binding Effects 0.000 claims description 11
- 108020005202 Viral DNA Proteins 0.000 claims description 9
- 108020005196 Mitochondrial DNA Proteins 0.000 claims description 8
- 210000004102 animal cell Anatomy 0.000 claims description 8
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 8
- 210000005253 yeast cell Anatomy 0.000 claims description 7
- 101000709520 Chlamydia trachomatis serovar L2 (strain 434/Bu / ATCC VR-902B) Atypical response regulator protein ChxR Proteins 0.000 claims description 2
- 108091006107 transcriptional repressors Proteins 0.000 claims description 2
- 108091029865 Exogenous DNA Proteins 0.000 claims 2
- 102100025169 Max-binding protein MNT Human genes 0.000 claims 1
- 238000010362 genome editing Methods 0.000 abstract description 15
- 230000033228 biological regulation Effects 0.000 abstract description 11
- 102000053602 DNA Human genes 0.000 description 135
- 235000018102 proteins Nutrition 0.000 description 83
- 230000000694 effects Effects 0.000 description 63
- 230000027455 binding Effects 0.000 description 61
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 40
- 238000003776 cleavage reaction Methods 0.000 description 38
- 239000013612 plasmid Substances 0.000 description 38
- 230000007017 scission Effects 0.000 description 38
- 241000588650 Neisseria meningitidis Species 0.000 description 33
- 230000008685 targeting Effects 0.000 description 29
- 238000003556 assay Methods 0.000 description 27
- 230000035772 mutation Effects 0.000 description 27
- 230000006801 homologous recombination Effects 0.000 description 23
- 238000002744 homologous recombination Methods 0.000 description 23
- 239000000523 sample Substances 0.000 description 23
- 125000006850 spacer group Chemical group 0.000 description 20
- 241000894006 Bacteria Species 0.000 description 17
- 238000009826 distribution Methods 0.000 description 17
- 108091028113 Trans-activating crRNA Proteins 0.000 description 16
- 230000005782 double-strand break Effects 0.000 description 16
- 230000001404 mediated effect Effects 0.000 description 15
- 235000004279 alanine Nutrition 0.000 description 14
- 210000005260 human cell Anatomy 0.000 description 14
- 230000011559 double-strand break repair via nonhomologous end joining Effects 0.000 description 13
- 238000001890 transfection Methods 0.000 description 13
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 12
- 241000193996 Streptococcus pyogenes Species 0.000 description 12
- 241000589892 Treponema denticola Species 0.000 description 11
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 11
- 238000003780 insertion Methods 0.000 description 11
- 230000037431 insertion Effects 0.000 description 11
- 229920001184 polypeptide Polymers 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 238000013518 transcription Methods 0.000 description 10
- 230000035897 transcription Effects 0.000 description 10
- 239000013641 positive control Substances 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- 108060003760 HNH nuclease Proteins 0.000 description 8
- 102000029812 HNH nuclease Human genes 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 238000010166 immunofluorescence Methods 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 7
- 101000976622 Homo sapiens Zinc finger protein 42 homolog Proteins 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 239000012190 activator Substances 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 210000004962 mammalian cell Anatomy 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 238000011144 upstream manufacturing Methods 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 241000194020 Streptococcus thermophilus Species 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- 108091023037 Aptamer Proteins 0.000 description 5
- 238000010453 CRISPR/Cas method Methods 0.000 description 5
- 241000589602 Francisella tularensis Species 0.000 description 5
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 5
- 238000011529 RT qPCR Methods 0.000 description 5
- 102100023550 Zinc finger protein 42 homolog Human genes 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 238000005520 cutting process Methods 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 229940118764 francisella tularensis Drugs 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 229910001425 magnesium ion Inorganic materials 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 108091032955 Bacterial small RNA Proteins 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 230000007018 DNA scission Effects 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 4
- 108700008625 Reporter Genes Proteins 0.000 description 4
- 108700009124 Transcription Initiation Site Proteins 0.000 description 4
- 230000003044 adaptive effect Effects 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000001747 exhibiting effect Effects 0.000 description 4
- 239000013613 expression plasmid Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 108010054624 red fluorescent protein Proteins 0.000 description 4
- 230000008439 repair process Effects 0.000 description 4
- 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 4
- 230000009466 transformation Effects 0.000 description 4
- 241000203069 Archaea Species 0.000 description 3
- 108091079001 CRISPR RNA Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 102000016911 Deoxyribonucleases Human genes 0.000 description 3
- 108010053770 Deoxyribonucleases Proteins 0.000 description 3
- 108050008753 HNH endonucleases Proteins 0.000 description 3
- 102000000310 HNH endonucleases Human genes 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 101710125418 Major capsid protein Proteins 0.000 description 3
- 201000009906 Meningitis Diseases 0.000 description 3
- 241000588653 Neisseria Species 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 238000010459 TALEN Methods 0.000 description 3
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 3
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000012350 deep sequencing Methods 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 231100000219 mutagenic Toxicity 0.000 description 3
- 230000003505 mutagenic effect Effects 0.000 description 3
- 230000006780 non-homologous end joining Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229920002477 rna polymer Polymers 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241001515965 unidentified phage Species 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000589875 Campylobacter jejuni Species 0.000 description 2
- 101710132601 Capsid protein Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 241000193155 Clostridium botulinum Species 0.000 description 2
- 101710094648 Coat protein Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 241001485655 Corynebacterium glutamicum ATCC 13032 Species 0.000 description 2
- 241000423296 Gluconacetobacter diazotrophicus PA1 5 Species 0.000 description 2
- 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 2
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 2
- 108010015268 Integration Host Factors Proteins 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 2
- 101710141454 Nucleoprotein Proteins 0.000 description 2
- 101150085710 OCT4 gene Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 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 2
- 101710083689 Probable capsid protein Proteins 0.000 description 2
- 102000003661 Ribonuclease III Human genes 0.000 description 2
- 108010057163 Ribonuclease III Proteins 0.000 description 2
- 102000004389 Ribonucleoproteins Human genes 0.000 description 2
- 108010081734 Ribonucleoproteins Proteins 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- 241000194019 Streptococcus mutans Species 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 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 2
- 230000004721 adaptive immunity Effects 0.000 description 2
- 101150063416 add gene Proteins 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000008970 bacterial immunity Effects 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004061 bleaching Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 108091006047 fluorescent proteins Proteins 0.000 description 2
- 102000034287 fluorescent proteins Human genes 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000012165 high-throughput sequencing Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- -1 repressors Proteins 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000013515 script Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000037426 transcriptional repression Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 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 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 241001041760 Acidothermus cellulolyticus 11B Species 0.000 description 1
- 101710159080 Aconitate hydratase A Proteins 0.000 description 1
- 101710159078 Aconitate hydratase B Proteins 0.000 description 1
- 241000417230 Actinobacillus succinogenes 130Z Species 0.000 description 1
- 102100033647 Activity-regulated cytoskeleton-associated protein Human genes 0.000 description 1
- 241000778935 Akkermansia muciniphila ATCC BAA-835 Species 0.000 description 1
- 108091093088 Amplicon Proteins 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
- 241000186020 Bifidobacterium dentium 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
- 208000024172 Cardiovascular disease Diseases 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
- 108700010070 Codon Usage Proteins 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
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 1
- 102220605872 Cytosolic arginine sensor for mTORC1 subunit 2_D16A_mutation Human genes 0.000 description 1
- 230000006820 DNA synthesis 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
- 241001338691 Elusimicrobium minutum Species 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282326 Felis catus 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
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 241001453258 Helicobacter hepaticus Species 0.000 description 1
- 101001057565 Heliocidaris crassispina Exogastrula-inducing polypeptide Proteins 0.000 description 1
- 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 1
- 102100024594 Histone-lysine N-methyltransferase PRDM16 Human genes 0.000 description 1
- 101000686942 Homo sapiens Histone-lysine N-methyltransferase PRDM16 Proteins 0.000 description 1
- 101001012021 Homo sapiens Mammalian ependymin-related protein 1 Proteins 0.000 description 1
- 101000669640 Homo sapiens Mitochondrial import inner membrane translocase subunit TIM14 Proteins 0.000 description 1
- 101001094700 Homo sapiens POU domain, class 5, transcription factor 1 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
- 241000186869 Lactobacillus salivarius Species 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241001193656 Legionella pneumophila str. Paris Species 0.000 description 1
- 241000186805 Listeria innocua Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100030031 Mammalian ependymin-related protein 1 Human genes 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 241001378931 Methanococcus maripaludis C7 Species 0.000 description 1
- 102100039325 Mitochondrial import inner membrane translocase subunit TIM14 Human genes 0.000 description 1
- 241000699670 Mus sp. Species 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
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001648684 Nitrobacter hamburgensis X14 Species 0.000 description 1
- 241001037736 Nocardia farcinica IFM 10152 Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000601272 Parvibaculum lavamentivorans DS-1 Species 0.000 description 1
- 241000606856 Pasteurella multocida Species 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
- 101710086053 Putative endonuclease Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 101710105008 RNA-binding protein Proteins 0.000 description 1
- 238000003559 RNA-seq method Methods 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
- 241000516659 Roseiflexus Species 0.000 description 1
- 241000504328 Roseiflexus castenholzii DSM 13941 Species 0.000 description 1
- 241000826915 Saccharum officinarum complex Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 241000933177 Shewanella pealeana ATCC 700345 Species 0.000 description 1
- 241001496704 Slackia heliotrinireducens DSM 20476 Species 0.000 description 1
- 241001478880 Streptobacillus moniliformis 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
- 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
- 241000192593 Synechocystis sp. PCC 6803 Species 0.000 description 1
- 241001496699 Thermomonospora curvata DSM 43183 Species 0.000 description 1
- 241000589499 Thermus thermophilus Species 0.000 description 1
- 241000322994 Tolumonas auensis DSM 9187 Species 0.000 description 1
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 1
- 241000999858 Treponema denticola ATCC 35405 Species 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 241000847071 Verminephrobacter eiseniae EF01-2 Species 0.000 description 1
- 241000605939 Wolinella succinogenes Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 241000883281 [Clostridium] cellulolyticum H10 Species 0.000 description 1
- 241000714896 [Eubacterium] rectale ATCC 33656 Species 0.000 description 1
- 101150067314 aadA gene Proteins 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 210000003486 adipose tissue brown Anatomy 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 101150038500 cas9 gene Proteins 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 210000002304 esc Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 108010021843 fluorescent protein 583 Proteins 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 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
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000036438 mutation frequency Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000007481 next generation sequencing Methods 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229960000268 spectinomycin Drugs 0.000 description 1
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000023895 stem cell maintenance Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229940115920 streptococcus dysgalactiae Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2/00—Peptides of undefined number of amino acids; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3519—Fusion with another nucleic acid
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/33—Alteration of splicing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/50—Methods for regulating/modulating their activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/106—Plasmid DNA for vertebrates
- C12N2800/107—Plasmid DNA for vertebrates for mammalian
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/40—Systems of functionally co-operating 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/10—Vectors comprising a non-peptidic targeting moiety
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/34—Vector systems having a special element relevant for transcription being a transcription initiation element
-
- 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
- C12N2999/00—Further aspects of viruses or vectors not covered by groups C12N2710/00 - C12N2796/00 or C12N2800/00
- C12N2999/007—Technological advancements, e.g. new system for producing known virus, cre-lox system for production of transgenic animals
-
- 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)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361844844P | 2013-07-10 | 2013-07-10 | |
| US61/844.844 | 2013-07-10 | ||
| PCT/US2014/045700 WO2015006294A2 (en) | 2013-07-10 | 2014-07-08 | Orthogonal cas9 proteins for rna-guided gene regulation and editing |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112016000571A2 BR112016000571A2 (enExample) | 2017-07-25 |
| BR112016000571B1 true BR112016000571B1 (pt) | 2023-12-26 |
Family
ID=52280701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112016000571-6A BR112016000571B1 (pt) | 2013-07-10 | 2014-07-08 | Métodos in vitro para modular a expressão e para alterar um ou mais ácidos nucleicos alvo em uma célula simultaneamente com a regulação da expressão de um ou mais ácidos nucleicos alvo em uma célula, bem como célula de levedura ou bactéria compreendendo ácidos nucleicos |
Country Status (12)
| Country | Link |
|---|---|
| US (4) | US10329587B2 (enExample) |
| EP (2) | EP3666892A1 (enExample) |
| JP (3) | JP6718813B2 (enExample) |
| KR (2) | KR102285485B1 (enExample) |
| CN (2) | CN105517579B (enExample) |
| AU (4) | AU2014287397B2 (enExample) |
| BR (1) | BR112016000571B1 (enExample) |
| CA (2) | CA2917639C (enExample) |
| IL (3) | IL282489B (enExample) |
| RU (3) | RU2704981C2 (enExample) |
| SG (3) | SG11201600060VA (enExample) |
| WO (1) | WO2015006294A2 (enExample) |
Families Citing this family (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10030245B2 (en) | 2011-03-23 | 2018-07-24 | E I Du Pont De Nemours And Company | Methods for producing a complex transgenic trait locus |
| EP2734621B1 (en) | 2011-07-22 | 2019-09-04 | President and Fellows of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| SI3401400T1 (sl) | 2012-05-25 | 2019-10-30 | Univ California | Postopki in sestavki za RNA usmerjeno modifikacijo tarčne DNA in za RNA usmerjeno modulacijo prepisovanja |
| EP3138911B1 (en) | 2012-12-06 | 2018-12-05 | Sigma Aldrich Co. LLC | Crispr-based genome modification and regulation |
| DK3553174T3 (da) | 2012-12-17 | 2025-08-04 | Harvard College | Rna-guided modificering af humant genom |
| SG10201808935WA (en) | 2013-04-16 | 2018-11-29 | Regeneron Pharma | Targeted modification of rat genome |
| 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 |
| CA3109801C (en) | 2013-08-22 | 2024-01-09 | Andrew Cigan | Plant genome modification using guide rna/cas endonuclease systems and methods of use |
| US9340800B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | Extended DNA-sensing GRNAS |
| US9388430B2 (en) | 2013-09-06 | 2016-07-12 | President And Fellows Of Harvard College | Cas9-recombinase fusion proteins and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| ES2844174T3 (es) | 2013-09-18 | 2021-07-21 | Kymab Ltd | Métodos, células y organismos |
| CA2930015A1 (en) | 2013-11-07 | 2015-05-14 | Editas Medicine, Inc. | Crispr-related methods and compositions with governing grnas |
| WO2015070062A1 (en) * | 2013-11-07 | 2015-05-14 | Massachusetts Institute Of Technology | Cell-based genomic recorded accumulative memory |
| JP6174811B2 (ja) | 2013-12-11 | 2017-08-02 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ゲノムの標的改変のための方法及び組成物 |
| US9840699B2 (en) | 2013-12-12 | 2017-12-12 | President And Fellows Of Harvard College | Methods for nucleic acid editing |
| EP3114227B1 (en) | 2014-03-05 | 2021-07-21 | 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 |
| WO2015138510A1 (en) | 2014-03-10 | 2015-09-17 | Editas Medicine., Inc. | Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10) |
| US11339437B2 (en) | 2014-03-10 | 2022-05-24 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
| WO2015148863A2 (en) | 2014-03-26 | 2015-10-01 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating sickle cell disease |
| EP3126495A1 (en) | 2014-04-02 | 2017-02-08 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating primary open angle glaucoma |
| WO2016022363A2 (en) | 2014-07-30 | 2016-02-11 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| WO2016040030A1 (en) | 2014-09-12 | 2016-03-17 | E. I. Du Pont De Nemours And Company | Generation of site-specific-integration sites for complex trait loci in corn and soybean, and methods of use |
| AU2015330699B2 (en) | 2014-10-10 | 2021-12-02 | Editas Medicine, Inc. | Compositions and methods for promoting homology directed repair |
| GB201418965D0 (enExample) | 2014-10-24 | 2014-12-10 | Ospedale San Raffaele And Fond Telethon | |
| EP4464338A3 (en) | 2014-11-07 | 2025-02-12 | Editas Medicine, Inc. | Systems for improving crispr/cas-mediated genome-editing |
| CN107250148B (zh) | 2014-12-03 | 2021-04-16 | 安捷伦科技有限公司 | 具有化学修饰的指导rna |
| US9888673B2 (en) | 2014-12-10 | 2018-02-13 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| US10450576B2 (en) | 2015-03-27 | 2019-10-22 | E I Du Pont De Nemours And Company | Soybean U6 small nuclear RNA gene promoters and their use in constitutive expression of small RNA genes in plants |
| WO2016164356A1 (en) | 2015-04-06 | 2016-10-13 | The Board Of Trustees Of The Leland Stanford Junior University | Chemically modified guide rnas for crispr/cas-mediated gene regulation |
| US11180793B2 (en) * | 2015-04-24 | 2021-11-23 | Editas Medicine, Inc. | Evaluation of Cas9 molecule/guide RNA molecule complexes |
| JP7030522B2 (ja) | 2015-05-11 | 2022-03-07 | エディタス・メディシン、インコーポレイテッド | 幹細胞における遺伝子編集のための最適化crispr/cas9システムおよび方法 |
| CN107709562A (zh) | 2015-05-15 | 2018-02-16 | 先锋国际良种公司 | 指导rna/cas内切核酸酶系统 |
| CA2987927C (en) | 2015-06-01 | 2024-03-19 | Temple University - Of The Commonwealth System Of Higher Education | Methods and compositions for rna-guided treatment of hiv infection |
| 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 |
| WO2016205745A2 (en) * | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Cell sorting |
| WO2017023803A1 (en) | 2015-07-31 | 2017-02-09 | Regents Of The University Of Minnesota | Modified cells and methods of therapy |
| AU2016326711B2 (en) | 2015-09-24 | 2022-11-03 | Editas Medicine, Inc. | Use of exonucleases to improve CRISPR/Cas-mediated genome editing |
| IL258821B (en) | 2015-10-23 | 2022-07-01 | Harvard College | Nucleobase editors and their uses |
| WO2017074943A1 (en) * | 2015-10-27 | 2017-05-04 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of inducibly targeting chromatin effectors and compositions for use in the same |
| EP4163374A1 (en) | 2015-11-23 | 2023-04-12 | The Regents of the University of California | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 |
| EP3901258A1 (en) | 2016-01-11 | 2021-10-27 | The Board of Trustees of the Leland Stanford Junior University | Chimeric proteins and methods of immunotherapy |
| NZ743983A (en) | 2016-01-11 | 2025-08-29 | Univ Leland Stanford Junior | Chimeric proteins and methods of regulating gene expression |
| EP3402884A1 (en) * | 2016-01-15 | 2018-11-21 | Astrazeneca AB | Gene modification assays |
| US11512311B2 (en) | 2016-03-25 | 2022-11-29 | Editas Medicine, Inc. | Systems and methods for treating alpha 1-antitrypsin (A1AT) deficiency |
| WO2017165826A1 (en) | 2016-03-25 | 2017-09-28 | Editas Medicine, Inc. | Genome editing systems comprising repair-modulating enzyme molecules and methods of their use |
| US20190345259A1 (en) * | 2016-04-12 | 2019-11-14 | Synploid Biotek, Llc | Methods for creating synthetic chromosomes having gene regulatory systems and uses thereof |
| EP3442598B1 (en) | 2016-04-12 | 2025-02-19 | CarryGenes Bioengineering, LLC | Methods for creating synthetic chromosomes expressing biosynthetic pathways and uses thereof |
| EP4047092B1 (en) | 2016-04-13 | 2025-07-30 | 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 |
| US11779657B2 (en) | 2016-06-10 | 2023-10-10 | City Of Hope | Compositions and methods for mitochondrial genome editing |
| WO2018026976A1 (en) | 2016-08-02 | 2018-02-08 | Editas Medicine, Inc. | Compositions and methods for treating cep290 associated disease |
| KR20250103795A (ko) | 2016-08-03 | 2025-07-07 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 아데노신 핵염기 편집제 및 그의 용도 |
| CA3033327A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| CN106282228A (zh) * | 2016-08-19 | 2017-01-04 | 苏州兰希亚生物科技有限公司 | 一种基因点突变修复的方法 |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | 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 |
| JP7588390B2 (ja) | 2016-10-14 | 2024-11-22 | 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 | 核酸塩基エディターのaav送達 |
| CA3041068A1 (en) * | 2016-10-18 | 2018-04-26 | Regents Of The University Of Minnesota | Tumor infiltrating lymphocytes and methods of therapy |
| US20180245065A1 (en) | 2016-11-01 | 2018-08-30 | Novartis Ag | Methods and compositions for enhancing gene editing |
| WO2018119010A1 (en) | 2016-12-19 | 2018-06-28 | Editas Medicine, Inc. | Assessing nuclease cleavage |
| WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
| US12110545B2 (en) | 2017-01-06 | 2024-10-08 | Editas Medicine, Inc. | Methods of assessing nuclease cleavage |
| SG11201906795SA (en) * | 2017-01-28 | 2019-08-27 | Inari Agriculture Inc | Novel plant cells, plants, and seeds |
| TW201839136A (zh) | 2017-02-06 | 2018-11-01 | 瑞士商諾華公司 | 治療血色素異常症之組合物及方法 |
| WO2018148647A2 (en) * | 2017-02-10 | 2018-08-16 | Lajoie Marc Joseph | Genome editing reagents and their use |
| US10828330B2 (en) | 2017-02-22 | 2020-11-10 | IO Bioscience, Inc. | Nucleic acid constructs comprising gene editing multi-sites and uses thereof |
| AU2018225180B2 (en) * | 2017-02-22 | 2024-09-12 | Io Biosciences, Inc. | Nucleic acid constructs comprising gene editing multi-sites and uses thereof |
| CN110662556A (zh) | 2017-03-09 | 2020-01-07 | 哈佛大学的校长及成员们 | 癌症疫苗 |
| WO2018165504A1 (en) | 2017-03-09 | 2018-09-13 | 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 |
| EP3596217A1 (en) | 2017-03-14 | 2020-01-22 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| US11332727B2 (en) * | 2017-03-14 | 2022-05-17 | The Regents Of The University Of California | Method for reducing an immune response by administering an immune evading adeno-associated AAV8 or AAVDJ viral vector |
| BR112019019655A2 (pt) | 2017-03-23 | 2020-04-22 | Harvard College | editores de nucleobase que compreendem proteínas de ligação a dna programáveis por ácido nucleico |
| KR102758434B1 (ko) * | 2017-03-30 | 2025-01-21 | 고쿠리츠 다이가쿠 호진 교토 다이가쿠 | 게놈 편집에 의한 엑손 스키핑 유도 방법 |
| CN111031790A (zh) | 2017-04-20 | 2020-04-17 | E开创生物技术股份有限公司 | 产生基因修改的动物的方法 |
| EP3615672A1 (en) | 2017-04-28 | 2020-03-04 | Editas Medicine, Inc. | Methods and systems for analyzing guide rna molecules |
| AU2018265022A1 (en) | 2017-05-10 | 2019-11-21 | 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 |
| 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 |
| KR102746733B1 (ko) | 2017-06-09 | 2024-12-24 | 에디타스 메디신, 인코포레이티드 | 조작된 cas9 뉴클레아제 |
| WO2019003193A1 (en) | 2017-06-30 | 2019-01-03 | Novartis Ag | METHODS FOR TREATING DISEASES USING GENE EDITING SYSTEMS |
| JP2020530307A (ja) | 2017-06-30 | 2020-10-22 | インティマ・バイオサイエンス,インコーポレーテッド | 遺伝子治療のためのアデノ随伴ウイルスベクター |
| EP3652312A1 (en) | 2017-07-14 | 2020-05-20 | 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 |
| US11319532B2 (en) | 2017-08-30 | 2022-05-03 | President And Fellows Of Harvard College | High efficiency base editors comprising Gam |
| KR102338449B1 (ko) | 2017-09-21 | 2021-12-10 | 더 브로드 인스티튜트, 인코퍼레이티드 | 표적화된 핵산 편집을 위한 시스템, 방법, 및 조성물 |
| US11603536B2 (en) | 2017-09-29 | 2023-03-14 | Inari Agriculture Technology, Inc. | Methods for efficient maize genome editing |
| KR20250107288A (ko) | 2017-10-16 | 2025-07-11 | 더 브로드 인스티튜트, 인코퍼레이티드 | 아데노신 염기 편집제의 용도 |
| WO2019089803A1 (en) | 2017-10-31 | 2019-05-09 | The Broad Institute, Inc. | Methods and compositions for studying cell evolution |
| WO2019087113A1 (en) | 2017-11-01 | 2019-05-09 | Novartis Ag | Synthetic rnas and methods of use |
| JP2021502097A (ja) * | 2017-11-10 | 2021-01-28 | ユニバーシティ オブ マサチューセッツ | 標的化crispr送達プラットフォーム |
| WO2019118949A1 (en) | 2017-12-15 | 2019-06-20 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| BR112020014168A2 (pt) | 2018-01-12 | 2020-12-08 | Basf Se | Proteína, ácido nucleico isolado, gene recombinante, vetor, célula hospedeira, planta, parte de planta ou semente de trigo, métodos para produzir, produto de trigo, farinha, farelo integral, amido, grânulos de amido ou farelo de trigo e métodos para identificar e/ou selecionar uma planta de trigo |
| US12084676B2 (en) | 2018-02-23 | 2024-09-10 | Pioneer Hi-Bred International, Inc. | Cas9 orthologs |
| CA3093702A1 (en) | 2018-03-14 | 2019-09-19 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| CN116349651A (zh) | 2018-03-19 | 2023-06-30 | 瑞泽恩制药公司 | 使用crispr/cas系统对动物进行转录调制 |
| JP6614622B2 (ja) * | 2018-04-17 | 2019-12-04 | 国立大学法人名古屋大学 | 植物ゲノム編集方法 |
| CN117534769A (zh) | 2018-04-19 | 2024-02-09 | 加利福尼亚大学董事会 | 用于基因编辑的组合物和方法 |
| WO2019226953A1 (en) | 2018-05-23 | 2019-11-28 | The Broad Institute, Inc. | Base editors and uses thereof |
| AU2019291918B2 (en) | 2018-06-29 | 2025-06-12 | Editas Medicine, Inc. | Synthetic guide molecules, compositions and methods relating thereto |
| GB201813011D0 (en) | 2018-08-10 | 2018-09-26 | Vib Vzw | Means and methods for drought tolerance in crops |
| WO2020051562A2 (en) | 2018-09-07 | 2020-03-12 | Beam Therapeutics Inc. | Compositions and methods for improving base editing |
| WO2020092453A1 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Nucleobase editors comprising geocas9 and uses thereof |
| WO2020123887A2 (en) | 2018-12-14 | 2020-06-18 | Pioneer Hi-Bred International, Inc. | Novel crispr-cas systems for genome editing |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| EP3696189A1 (en) * | 2019-02-14 | 2020-08-19 | European Molecular Biology Laboratory | Means and methods for preparing engineered target proteins by genetic code expansion in a target protein selective manner |
| EP3942042A1 (en) | 2019-03-19 | 2022-01-26 | The Broad Institute, Inc. | Methods and compositions for editing nucleotide sequences |
| EP3956349A1 (en) | 2019-04-17 | 2022-02-23 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| US20210095273A1 (en) * | 2019-09-30 | 2021-04-01 | Sigma-Aldrich Co. Llc | Modulation of microbiota compositions using targeted nucleases |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| JP2023508731A (ja) * | 2019-12-30 | 2023-03-03 | ライフエディット セラピューティクス,インコーポレイティド | Rna誘導ヌクレアーゼ、その活性断片および多様体、ならびに使用方法 |
| JP7525140B2 (ja) * | 2020-01-31 | 2024-07-30 | 国立大学法人京都大学 | タンパク質翻訳の制御システム |
| WO2021226558A1 (en) | 2020-05-08 | 2021-11-11 | The Broad Institute, Inc. | Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence |
| GB202007943D0 (en) * | 2020-05-27 | 2020-07-08 | Snipr Biome Aps | Products & methods |
| RU2749307C1 (ru) * | 2020-10-30 | 2021-06-08 | Федеральное государственное бюджетное научное учреждение "Всероссийский научно-исследовательский институт сельскохозяйственной биотехнологии" (ФГБНУ ВНИИСБ) | Новая компактная нуклеаза CAS9 II типа из Anoxybacillus flavithermus |
| WO2022116139A1 (zh) * | 2020-12-04 | 2022-06-09 | 中国科学院脑科学与智能技术卓越创新中心 | 一种检测细胞内源性低丰度基因和lncRNA水平的方法 |
| US12171813B2 (en) | 2021-02-05 | 2024-12-24 | Christiana Care Gene Editing Institute, Inc. | Methods of and compositions for reducing gene expression and/or activity |
| US11884915B2 (en) | 2021-09-10 | 2024-01-30 | Agilent Technologies, Inc. | Guide RNAs with chemical modification for prime editing |
| MX2024005318A (es) | 2021-11-01 | 2024-09-23 | Tome Biosciences Inc | Plataforma de construccion unica para el suministro simultaneo de maquinaria de edicion de genes y carga de acido nucleico. |
| IL313765A (en) | 2021-12-22 | 2024-08-01 | Tome Biosciences Inc | Joint provision of a gene editor structure 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 |
| WO2025224107A1 (en) | 2024-04-22 | 2025-10-30 | 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 (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6933378B2 (en) * | 1997-05-30 | 2005-08-23 | Joseph Atabekov | Methods for coexpression of more than one gene in eukaryotic cells |
| US6203986B1 (en) | 1998-10-22 | 2001-03-20 | Robert H. Singer | Visualization of RNA in living cells |
| RU2467069C2 (ru) * | 2006-03-09 | 2012-11-20 | Зе Скрипс Ресеч Инститьют | Система экспрессии компонентов ортогональной трансляции в эубактериальной клетке-хозяине |
| EP2518155B1 (en) * | 2006-08-04 | 2014-07-23 | Georgia State University Research Foundation, Inc. | Enzyme sensors, methods for preparing and using such sensors, and methods of detecting protease activity |
| RU2531343C2 (ru) | 2007-03-02 | 2014-10-20 | ДюПон Ньютришн Байосайенсиз АпС, | Способ генерирования заквасочной культуры, заквасочная культура и способ ферментации с ее использованием |
| 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 |
| CN103038338B (zh) | 2010-05-10 | 2017-03-08 | 加利福尼亚大学董事会 | 核糖核酸内切酶组合物及其使用方法 |
| CN103025344B (zh) | 2010-05-17 | 2016-06-29 | 桑格摩生物科学股份有限公司 | 新型dna-结合蛋白及其用途 |
| WO2012164565A1 (en) | 2011-06-01 | 2012-12-06 | Yeda Research And Development Co. Ltd. | Compositions and methods for downregulating prokaryotic genes |
| EP2734621B1 (en) * | 2011-07-22 | 2019-09-04 | President and Fellows of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| GB201122458D0 (en) * | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
| SG10201606959PA (en) | 2012-02-24 | 2016-09-29 | Hutchinson Fred Cancer Res | Compositions and methods for the treatment of hemoglobinopathies |
| MX374399B (es) | 2012-02-29 | 2025-03-06 | Sangamo Biosciences Inc | Composiciones y sus usos para tratar y prevenir la enfermedad de huntington. |
| US9637739B2 (en) | 2012-03-20 | 2017-05-02 | Vilnius University | RNA-directed DNA cleavage by the Cas9-crRNA complex |
| WO2013141680A1 (en) | 2012-03-20 | 2013-09-26 | Vilnius University | RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX |
| SI3401400T1 (sl) * | 2012-05-25 | 2019-10-30 | Univ California | Postopki in sestavki za RNA usmerjeno modifikacijo tarčne DNA in za RNA usmerjeno modulacijo prepisovanja |
| HK1207111A1 (en) | 2012-08-03 | 2016-01-22 | 加利福尼亚大学董事会 | Methods and compositions for controlling gene expression by rna processing |
| EP3138911B1 (en) * | 2012-12-06 | 2018-12-05 | Sigma Aldrich Co. LLC | Crispr-based genome modification and regulation |
| 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 |
| 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 |
| DK3553174T3 (da) * | 2012-12-17 | 2025-08-04 | Harvard College | Rna-guided modificering af humant genom |
| KR20230136697A (ko) * | 2013-06-05 | 2023-09-26 | 듀크 유니버시티 | Rna-가이드 유전자 편집 및 유전자 조절 |
-
2014
- 2014-07-08 SG SG11201600060VA patent/SG11201600060VA/en unknown
- 2014-07-08 RU RU2016104161A patent/RU2704981C2/ru active
- 2014-07-08 EP EP19219620.2A patent/EP3666892A1/en active Pending
- 2014-07-08 SG SG10201800213VA patent/SG10201800213VA/en unknown
- 2014-07-08 RU RU2019132195A patent/RU2748433C2/ru active
- 2014-07-08 CA CA2917639A patent/CA2917639C/en active Active
- 2014-07-08 WO PCT/US2014/045700 patent/WO2015006294A2/en not_active Ceased
- 2014-07-08 US US14/903,728 patent/US10329587B2/en active Active
- 2014-07-08 AU AU2014287397A patent/AU2014287397B2/en active Active
- 2014-07-08 EP EP14823626.8A patent/EP3019204B1/en active Active
- 2014-07-08 KR KR1020167003074A patent/KR102285485B1/ko active Active
- 2014-07-08 CN CN201480048712.9A patent/CN105517579B/zh active Active
- 2014-07-08 CA CA3218040A patent/CA3218040A1/en active Pending
- 2014-07-08 BR BR112016000571-6A patent/BR112016000571B1/pt active IP Right Grant
- 2014-07-08 CN CN201910999512.6A patent/CN110819658B/zh active Active
- 2014-07-08 JP JP2016525414A patent/JP6718813B2/ja active Active
- 2014-07-08 KR KR1020217024118A patent/KR102481330B1/ko active Active
- 2014-07-08 IL IL282489A patent/IL282489B/en unknown
- 2014-07-08 SG SG10201913015XA patent/SG10201913015XA/en unknown
-
2015
- 2015-03-31 US US14/674,895 patent/US9587252B2/en active Active
-
2016
- 2016-01-06 IL IL24347616A patent/IL243476B/en active IP Right Grant
-
2019
- 2019-05-14 US US16/411,793 patent/US11649469B2/en active Active
- 2019-10-29 IL IL270259A patent/IL270259B/en active IP Right Grant
- 2019-12-27 JP JP2019238875A patent/JP7153992B2/ja active Active
-
2020
- 2020-01-09 AU AU2020200163A patent/AU2020200163C1/en active Active
-
2021
- 2021-05-20 RU RU2021114286A patent/RU2771583C1/ru active
- 2021-11-25 AU AU2021273624A patent/AU2021273624C1/en active Active
-
2022
- 2022-10-03 JP JP2022159833A patent/JP2022176275A/ja active Pending
-
2023
- 2023-04-06 US US18/296,446 patent/US20230257781A1/en active Pending
-
2024
- 2024-10-28 AU AU2024227690A patent/AU2024227690A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230257781A1 (en) | Orthogonal Cas9 Proteins for RNA-Guided Gene Regulation and Editing | |
| HK40031893A (en) | Orthogonal cas9 proteins for rna-guided gene regulation and editing | |
| HK1217907B (en) | Orthogonal cas9 proteins for rna-guided gene regulation and editing | |
| NZ754836B2 (en) | Orthogonal cas9 proteins for rna-guided gene regulation and editing | |
| NZ754837B2 (en) | Orthogonal cas9 proteins for rna-guided gene regulation and editing | |
| NZ716605B2 (en) | Orthogonal cas9 proteins for rna-guided gene regulation and editing | |
| BR112015030491B1 (pt) | Método para modular a expressão de um ácido nucleico alvo em uma célula |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] |
Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI |
|
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B350 | Update of information on the portal [chapter 15.35 patent gazette] | ||
| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B06G | Technical and formal requirements: other requirements [chapter 6.7 patent gazette] | ||
| B06I | Publication of requirement cancelled [chapter 6.9 patent gazette] |
Free format text: ANULADA A PUBLICACAO CODIGO 6.7 NA RPI NO 2733 DE 23/05/2023 POR TER SIDO INDEVIDA. |
|
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 08/07/2014, OBSERVADAS AS CONDICOES LEGAIS |