AU2014273091B2 - A LAGLIDADG homing endonuclease cleaving the T cell receptor alpha gene and uses thereof - Google Patents
A LAGLIDADG homing endonuclease cleaving the T cell receptor alpha gene and uses thereof Download PDFInfo
- Publication number
- AU2014273091B2 AU2014273091B2 AU2014273091A AU2014273091A AU2014273091B2 AU 2014273091 B2 AU2014273091 B2 AU 2014273091B2 AU 2014273091 A AU2014273091 A AU 2014273091A AU 2014273091 A AU2014273091 A AU 2014273091A AU 2014273091 B2 AU2014273091 B2 AU 2014273091B2
- Authority
- AU
- Australia
- Prior art keywords
- cell
- cells
- dna
- sequence
- seq
- 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
- 108010042407 Endonucleases Proteins 0.000 title claims abstract description 122
- 102000004533 Endonucleases Human genes 0.000 title abstract description 26
- 108091008874 T cell receptors Proteins 0.000 title description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title description 3
- 101150087698 alpha gene Proteins 0.000 title description 2
- 239000013598 vector Substances 0.000 claims abstract description 61
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 22
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 22
- 239000002157 polynucleotide Substances 0.000 claims abstract description 22
- 210000004027 cell Anatomy 0.000 claims description 179
- 108090000623 proteins and genes Proteins 0.000 claims description 138
- 108020004414 DNA Proteins 0.000 claims description 108
- 102100031780 Endonuclease Human genes 0.000 claims description 94
- 150000007523 nucleic acids Chemical group 0.000 claims description 82
- 238000000034 method Methods 0.000 claims description 76
- 102000004169 proteins and genes Human genes 0.000 claims description 73
- 230000000694 effects Effects 0.000 claims description 60
- 102100029452 T cell receptor alpha chain constant Human genes 0.000 claims description 54
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 54
- 102000039446 nucleic acids Human genes 0.000 claims description 46
- 108020004707 nucleic acids Proteins 0.000 claims description 46
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 45
- 230000007017 scission Effects 0.000 claims description 44
- 238000003776 cleavage reaction Methods 0.000 claims description 43
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 43
- 238000005520 cutting process Methods 0.000 claims description 35
- 101710163270 Nuclease Proteins 0.000 claims description 32
- 108060002716 Exonuclease Proteins 0.000 claims description 31
- 102000013165 exonuclease Human genes 0.000 claims description 31
- 239000011159 matrix material Substances 0.000 claims description 30
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 30
- 229920001184 polypeptide Polymers 0.000 claims description 26
- 102000004190 Enzymes Human genes 0.000 claims description 25
- 108090000790 Enzymes Proteins 0.000 claims description 25
- 230000003197 catalytic effect Effects 0.000 claims description 24
- 108020001580 protein domains Proteins 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 238000006467 substitution reaction Methods 0.000 claims description 16
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 15
- 230000035772 mutation Effects 0.000 claims description 15
- 231100000350 mutagenesis Toxicity 0.000 claims description 14
- 238000012545 processing Methods 0.000 claims description 14
- 238000002703 mutagenesis Methods 0.000 claims description 13
- 239000000427 antigen Substances 0.000 claims description 12
- 108091007433 antigens Proteins 0.000 claims description 12
- 102000036639 antigens Human genes 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 11
- 108700019146 Transgenes Proteins 0.000 claims description 10
- 101000830950 Homo sapiens Three prime repair exonuclease 2 Proteins 0.000 claims description 9
- 108091007494 Nucleic acid- binding domains Proteins 0.000 claims description 8
- 102100024872 Three prime repair exonuclease 2 Human genes 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 8
- 229910052725 zinc Inorganic materials 0.000 claims description 8
- 239000011701 zinc Substances 0.000 claims description 8
- 230000001965 increasing effect Effects 0.000 claims description 7
- 230000011664 signaling Effects 0.000 claims description 7
- 108091006047 fluorescent proteins Proteins 0.000 claims description 6
- 102000034287 fluorescent proteins Human genes 0.000 claims description 6
- 210000003705 ribosome Anatomy 0.000 claims description 6
- 102100034343 Integrase Human genes 0.000 claims description 5
- 108060004795 Methyltransferase Proteins 0.000 claims description 5
- 101100508818 Mus musculus Inpp5k gene Proteins 0.000 claims description 5
- 101100366438 Rattus norvegicus Sphkap gene Proteins 0.000 claims description 5
- 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 description 4
- 108010061833 Integrases Proteins 0.000 claims description 4
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 3
- 102000003960 Ligases Human genes 0.000 claims description 3
- 108090000364 Ligases Proteins 0.000 claims description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 claims description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 claims description 3
- 108091000080 Phosphotransferase Proteins 0.000 claims description 3
- 102000018120 Recombinases Human genes 0.000 claims description 3
- 108010091086 Recombinases Proteins 0.000 claims description 3
- 101710183280 Topoisomerase Proteins 0.000 claims description 3
- 102000008579 Transposases Human genes 0.000 claims description 3
- 108010020764 Transposases Proteins 0.000 claims description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 3
- 102000020233 phosphotransferase Human genes 0.000 claims description 3
- 101000634853 Homo sapiens T cell receptor alpha chain constant Proteins 0.000 claims description 2
- 210000003738 lymphoid progenitor cell Anatomy 0.000 claims 1
- 241000282414 Homo sapiens Species 0.000 abstract description 32
- 108700042076 T-Cell Receptor alpha Genes Proteins 0.000 abstract description 9
- 239000000203 mixture Substances 0.000 abstract description 9
- 230000001225 therapeutic effect Effects 0.000 abstract description 9
- 230000000415 inactivating effect Effects 0.000 abstract 1
- 102000053602 DNA Human genes 0.000 description 104
- 235000018102 proteins Nutrition 0.000 description 61
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 55
- 230000014509 gene expression Effects 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 24
- 230000000670 limiting effect Effects 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 21
- 150000001413 amino acids Chemical class 0.000 description 21
- 230000008685 targeting Effects 0.000 description 20
- 108020004999 messenger RNA Proteins 0.000 description 19
- 125000003729 nucleotide group Chemical group 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 238000002744 homologous recombination Methods 0.000 description 18
- 230000006801 homologous recombination Effects 0.000 description 18
- 239000002773 nucleotide Substances 0.000 description 18
- 102000037865 fusion proteins Human genes 0.000 description 16
- 108020001507 fusion proteins Proteins 0.000 description 16
- 230000006780 non-homologous end joining Effects 0.000 description 16
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 14
- 229920002477 rna polymer Polymers 0.000 description 14
- 239000000758 substrate Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- 210000000130 stem cell Anatomy 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 12
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 12
- 238000000684 flow cytometry Methods 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 101000634835 Homo sapiens M1-specific T cell receptor alpha chain Proteins 0.000 description 11
- 101000634836 Homo sapiens T cell receptor alpha chain MC.7.G5 Proteins 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 238000012217 deletion Methods 0.000 description 11
- 230000037430 deletion Effects 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 235000009697 arginine Nutrition 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 238000004520 electroporation Methods 0.000 description 10
- 238000010362 genome editing Methods 0.000 description 10
- 239000004475 Arginine Substances 0.000 description 9
- 230000004568 DNA-binding Effects 0.000 description 9
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 9
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 235000018977 lysine Nutrition 0.000 description 9
- 239000004472 Lysine Substances 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 208000036142 Viral infection Diseases 0.000 description 8
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 108091005948 blue fluorescent proteins Proteins 0.000 description 8
- 210000001161 mammalian embryo Anatomy 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000009385 viral infection Effects 0.000 description 8
- 101000582254 Homo sapiens Nuclear receptor corepressor 2 Proteins 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 230000005782 double-strand break Effects 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 230000008439 repair process Effects 0.000 description 7
- 108700028369 Alleles Proteins 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 6
- 210000005260 human cell Anatomy 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 230000032965 negative regulation of cell volume Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 230000000735 allogeneic effect Effects 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 235000009582 asparagine Nutrition 0.000 description 5
- 229960001230 asparagine Drugs 0.000 description 5
- 238000002619 cancer immunotherapy Methods 0.000 description 5
- 230000002759 chromosomal effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 238000010363 gene targeting Methods 0.000 description 5
- 208000024908 graft versus host disease Diseases 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 230000004960 subcellular localization Effects 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- 101000927313 Homo sapiens DNA replication ATP-dependent helicase DNA2 Proteins 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 238000002659 cell therapy Methods 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000003752 polymerase chain reaction Methods 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 239000012114 Alexa Fluor 647 Substances 0.000 description 3
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 3
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 3
- 230000033616 DNA repair Effects 0.000 description 3
- 230000007018 DNA scission Effects 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 108010059724 Micrococcal Nuclease Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 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 3
- 230000009471 action Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 210000004700 fetal blood Anatomy 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000005304 joining Methods 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 238000002708 random mutagenesis Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 210000003289 regulatory T cell Anatomy 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 108010068698 spleen exonuclease Proteins 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 101100370338 Bos taurus TREX1 gene Proteins 0.000 description 2
- 108020004638 Circular DNA Proteins 0.000 description 2
- 102100033072 DNA replication ATP-dependent helicase DNA2 Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- 108090000652 Flap endonucleases Proteins 0.000 description 2
- 102000004150 Flap endonucleases Human genes 0.000 description 2
- 101000830956 Homo sapiens Three-prime repair exonuclease 1 Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 101100370340 Mus musculus Trex1 gene Proteins 0.000 description 2
- 102000013901 Nucleoside diphosphate kinase Human genes 0.000 description 2
- 108700023477 Nucleoside diphosphate kinases Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 241000709664 Picornaviridae Species 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 102100024855 Three-prime repair exonuclease 1 Human genes 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 241000589634 Xanthomonas Species 0.000 description 2
- 101710185494 Zinc finger protein Proteins 0.000 description 2
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 2
- SAZUGELZHZOXHB-UHFFFAOYSA-N acecarbromal Chemical compound CCC(Br)(CC)C(=O)NC(=O)NC(C)=O SAZUGELZHZOXHB-UHFFFAOYSA-N 0.000 description 2
- 210000004504 adult stem cell Anatomy 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 108020001778 catalytic domains Proteins 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 150000004000 hexols Chemical class 0.000 description 2
- -1 hosphatase Proteins 0.000 description 2
- 102000045960 human DNA2 Human genes 0.000 description 2
- 102000054586 human TREX2 Human genes 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229940124589 immunosuppressive drug Drugs 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 244000000003 plant pathogen Species 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 210000004986 primary T-cell Anatomy 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 230000003007 single stranded DNA break Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 108010036169 three prime repair exonuclease 1 Proteins 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 210000003014 totipotent stem cell Anatomy 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 241000710189 Aphthovirus Species 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101001137540 Bos taurus Endonuclease G, mitochondrial Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000244202 Caenorhabditis Species 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108091060290 Chromatid Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010073254 Colicins Proteins 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 230000007064 DNA hydrolysis Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101710204468 Endonuclease YncB Proteins 0.000 description 1
- 101000876382 Enterobacteria phage T3 Endodeoxyribonuclease 1 Proteins 0.000 description 1
- 241000283087 Equus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102000002241 Eukaryotic Initiation Factors Human genes 0.000 description 1
- 108010014863 Eukaryotic Initiation Factors Proteins 0.000 description 1
- 108010007577 Exodeoxyribonuclease I Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 208000000666 Fowlpox Diseases 0.000 description 1
- 240000005702 Galium aparine Species 0.000 description 1
- 235000014820 Galium aparine Nutrition 0.000 description 1
- 241000287826 Gallus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000941423 Grom virus Species 0.000 description 1
- 108091027874 Group I catalytic intron Proteins 0.000 description 1
- 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001137538 Homo sapiens Endonuclease G, mitochondrial Proteins 0.000 description 1
- 101000979629 Homo sapiens Nucleoside diphosphate kinase A Proteins 0.000 description 1
- 101000836339 Homo sapiens Transposon Hsmar1 transposase Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 241000288145 Meleagris Species 0.000 description 1
- 241000288147 Meleagris gallopavo Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 101150101095 Mmp12 gene Proteins 0.000 description 1
- 101000836313 Moraxella sp Type II restriction enzyme MspI Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000714209 Norwalk virus Species 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 102100023252 Nucleoside diphosphate kinase A Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 241000277334 Oncorhynchus Species 0.000 description 1
- 241000277275 Oncorhynchus mykiss Species 0.000 description 1
- 241000144580 Ophiostoma novo-ulmi Species 0.000 description 1
- 241000702244 Orthoreovirus Species 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 108010010677 Phosphodiesterase I Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000232299 Ralstonia Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 101100404456 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YNK1 gene Proteins 0.000 description 1
- 241000277263 Salmo Species 0.000 description 1
- 241000277289 Salmo salar Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 101000965899 Simian virus 40 Large T antigen Proteins 0.000 description 1
- 241000713675 Spumavirus Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 108700039575 Three prime repair exonuclease 2 Proteins 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102100027172 Transposon Hsmar1 transposase Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000000961 alloantigen Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 150000001484 arginines Chemical class 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 208000004668 avian leukosis Diseases 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- JQXXHWHPUNPDRT-YOPQJBRCSA-N chembl1332716 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CCN(C)CC1 JQXXHWHPUNPDRT-YOPQJBRCSA-N 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 210000004756 chromatid Anatomy 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000012350 deep sequencing Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000002961 echo contrast media Substances 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002616 endonucleolytic effect Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 108010052305 exodeoxyribonuclease III Proteins 0.000 description 1
- 230000001036 exonucleolytic effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 108010055863 gene b exonuclease Proteins 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 231100000025 genetic toxicology Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 230000005182 global health Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 108010002685 hygromycin-B kinase Proteins 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000021005 inheritance pattern Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 101150054576 ndk1 gene Proteins 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004492 nuclear pore Anatomy 0.000 description 1
- 230000025308 nuclear transport Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 108010085336 phosphoribosyl-AMP cyclohydrolase Proteins 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 101150013092 rps3 gene Proteins 0.000 description 1
- 102220278926 rs759871071 Human genes 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000009258 tissue cross reactivity Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 235000021247 β-casein Nutrition 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA201370303 | 2013-05-31 | ||
| DKPA201370303 | 2013-05-31 | ||
| PCT/EP2014/061189 WO2014191527A1 (en) | 2013-05-31 | 2014-05-28 | A laglidadg homing endonuclease cleaving the t cell receptor alpha gene and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2014273091A1 AU2014273091A1 (en) | 2015-12-03 |
| AU2014273091B2 true AU2014273091B2 (en) | 2019-12-12 |
Family
ID=48628226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2014273091A Active AU2014273091B2 (en) | 2013-05-31 | 2014-05-28 | A LAGLIDADG homing endonuclease cleaving the T cell receptor alpha gene and uses thereof |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US10000746B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3004338B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6450371B2 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2014273091B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2913872C (cg-RX-API-DMAC7.html) |
| DK (1) | DK3004338T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2716867T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2014191527A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (78)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3320910A1 (en) * | 2011-04-05 | 2018-05-16 | Cellectis | Method for the generation of compact tale-nucleases and uses thereof |
| CA2853829C (en) | 2011-07-22 | 2023-09-26 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| 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 |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| US9388430B2 (en) | 2013-09-06 | 2016-07-12 | President And Fellows Of Harvard College | Cas9-recombinase fusion proteins and uses thereof |
| CN111218447B (zh) | 2013-11-07 | 2024-10-11 | 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 |
| US20150166982A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting pi3k point mutations |
| EP3092049A1 (en) | 2014-01-08 | 2016-11-16 | Flodesign Sonics Inc. | Acoustophoresis device with dual acoustophoretic chamber |
| EP3177718B1 (en) | 2014-07-30 | 2022-03-16 | President and Fellows of Harvard College | Cas9 proteins including ligand-dependent inteins |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| KR20250013291A (ko) | 2015-10-05 | 2025-01-31 | 프리시젼 바이오사이언시스 인코포레이티드 | 변형된 인간 t 세포 수용체 알파 불변 영역 유전자를 포함하는 유전자 변형된 세포 |
| EP3940070A1 (en) * | 2015-10-05 | 2022-01-19 | Precision Biosciences, Inc. | Engineered meganucleases with recognition sequences found in the human t cell receptor alpha constant region gene |
| SG11201803173VA (en) | 2015-10-23 | 2018-05-30 | Harvard College | Nucleobase editors and uses thereof |
| CN108699557B (zh) | 2015-12-04 | 2025-08-15 | 诺华股份有限公司 | 用于免疫肿瘤学的组合物和方法 |
| CN109311984A (zh) * | 2016-03-11 | 2019-02-05 | 蓝鸟生物公司 | 基因组编辑的免疫效应细胞 |
| US10188749B2 (en) | 2016-04-14 | 2019-01-29 | Fred Hutchinson Cancer Research Center | Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers |
| NZ748378A (en) * | 2016-04-14 | 2025-08-29 | Fred Hutchinson Cancer Center | Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| AU2017301609A1 (en) * | 2016-07-25 | 2019-02-21 | Bluebird Bio, Inc. | BCL11A homing endonuclease variants, compositions, and methods of use |
| JP7231935B2 (ja) | 2016-08-03 | 2023-03-08 | 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 | アデノシン核酸塩基編集因子およびそれらの使用 |
| CA3033327A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| CA3034094A1 (en) | 2016-08-16 | 2018-02-22 | Bluebird Bio, Inc. | Il-10 receptor alpha homing endonuclease variants, compositions, and methods of use |
| EP3504335A4 (en) * | 2016-08-23 | 2020-04-15 | Bluebird Bio, Inc. | HOMING TIM3 ENDONUCLEASE VARIANTS, COMPOSITIONS AND METHODS OF USE |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| CA3035455A1 (en) | 2016-09-08 | 2018-03-15 | Bluebird Bio, Inc. | Pd-1 homing endonuclease variants, compositions, and methods of use |
| MX2019004156A (es) * | 2016-10-11 | 2019-09-26 | Bluebird Bio Inc | Variantes de endonucleasa homing de receptor de linfocitos t alfa (tcralpha). |
| WO2018071868A1 (en) | 2016-10-14 | 2018-04-19 | President And Fellows Of Harvard College | Aav delivery of nucleobase editors |
| AU2017346683B2 (en) * | 2016-10-17 | 2024-04-18 | Regeneron Pharmaceuticals, Inc. | TGFβR2 endonuclease variants, compositions, and methods of use |
| WO2018073393A2 (en) | 2016-10-19 | 2018-04-26 | Cellectis | Tal-effector nuclease (talen) -modified allogenic cells suitable for therapy |
| IL266892B2 (en) | 2016-12-02 | 2025-10-01 | Univ Southern California | Artificial immune receptors and methods of using them |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| CN110121336A (zh) | 2017-01-05 | 2019-08-13 | 弗莱德哈钦森癌症研究中心 | 改善疫苗功效的系统和方法 |
| US12390514B2 (en) | 2017-03-09 | 2025-08-19 | President And Fellows Of Harvard College | Cancer vaccine |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | プレジデント アンド フェローズ オブ ハーバード カレッジ | シトシンからグアニンへの塩基編集因子 |
| CN110832075A (zh) | 2017-03-22 | 2020-02-21 | 诺华股份有限公司 | 用于免疫肿瘤学的组合物和方法 |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
| CA3059643A1 (en) | 2017-04-13 | 2018-10-18 | Cellectis | New sequence specific reagents targeting ccr5 in primary hematopoietic cells |
| 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 |
| JP7191042B2 (ja) * | 2017-05-25 | 2022-12-16 | ２セブンティ バイオ インコーポレイテッド | Ｃｂｌｂエンドヌクレアーゼバリアント、組成物、および使用方法 |
| CA3068465A1 (en) | 2017-06-30 | 2019-01-03 | Precision Biosciences, Inc. | Genetically-modified t cells comprising a modified intron in the t cell receptor alpha gene |
| EP3658573A1 (en) | 2017-07-28 | 2020-06-03 | President and Fellows of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (pace) |
| WO2019139645A2 (en) | 2017-08-30 | 2019-07-18 | President And Fellows Of Harvard College | High efficiency base editors comprising gam |
| WO2019070974A1 (en) * | 2017-10-04 | 2019-04-11 | Bluebird Bio, Inc. | PCSK9 ENDONUCLEASE VARIANTS, COMPOSITIONS AND METHODS OF USE |
| EP3702453A4 (en) * | 2017-10-10 | 2021-07-21 | Hiroshima University | TOTAL REPLACEMENT TECHNIQUE FOR T-LYMPHOCYTE RECEPTOR USING PLATINUM TALENE |
| TWI814745B (zh) | 2017-10-10 | 2023-09-11 | 國立大學法人廣島大學 | 使用效應T細胞(Teff)抗原受體之抗原特異性控制性T細胞(Treg)之製出技術 |
| AU2018352592C1 (en) | 2017-10-16 | 2025-09-25 | Beam Therapeutics, Inc. | Uses of adenosine base editors |
| JP2021507561A (ja) | 2017-12-14 | 2021-02-22 | フロデザイン ソニックス， インク．Ｆｌｏｄｅｓｉｇｎ Ｓｏｎｉｃｓ， Ｉｎｃ． | 音響トランスデューサドライバ及びコントローラ |
| EP3724214A4 (en) | 2017-12-15 | 2021-09-01 | The Broad Institute Inc. | SYSTEMS AND METHODS FOR PREDICTING REPAIR RESULTS IN GENETIC ENGINEERING |
| US20210002621A1 (en) * | 2017-12-20 | 2021-01-07 | Bluebird Bio, Inc. | Ctla4 homing endonuclease variants, compositions, and methods of use |
| IL277883B2 (en) | 2018-04-12 | 2023-12-01 | Prec Biosciences Inc | Optimized engineered nucleases having specificity for the human t cell receptor alpha constant region gene |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| AU2019287720B2 (en) | 2018-06-14 | 2025-08-28 | Regeneron Pharmaceuticals, Inc. | CD79A chimeric antigen receptors |
| WO2020072059A1 (en) | 2018-10-04 | 2020-04-09 | Bluebird Bio, Inc. | Cblb endonuclease variants, compositions, and methods of use |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| US12404500B2 (en) | 2018-12-10 | 2025-09-02 | Novo Nordisk A/S | Homing endonuclease variants |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| GB2601617B (en) | 2019-03-19 | 2024-02-21 | Broad Inst Inc | Methods and compositions for editing nucleotide sequences |
| KR20240122580A (ko) | 2019-04-03 | 2024-08-12 | 프리시젼 바이오사이언시스 인코포레이티드 | 마이크로RNA-적응 shRNA(shRNAmiR)를 포함하는 유전자-변형 면역 세포 |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| EP4004216A1 (en) | 2019-07-25 | 2022-06-01 | Precision BioSciences, Inc. | Compositions and methods for sequential stacking of nucleic acid sequences into a genomic locus |
| CA3148179A1 (en) | 2019-08-20 | 2021-02-25 | Bruce J. Mccreedy Jr. | Lymphodepletion dosing regimens for cellular immunotherapies |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| US20220411479A1 (en) | 2019-10-30 | 2022-12-29 | Precision Biosciences, Inc. | Cd20 chimeric antigen receptors and methods of use for immunotherapy |
| DE112021002672T5 (de) | 2020-05-08 | 2023-04-13 | President And Fellows Of Harvard College | Vefahren und zusammensetzungen zum gleichzeitigen editieren beider stränge einer doppelsträngigen nukleotid-zielsequenz |
| WO2022035793A1 (en) | 2020-08-10 | 2022-02-17 | Precision Biosciences, Inc. | Antibodies and fragments specific for b-cell maturation antigen and uses thereof |
| JP2024503249A (ja) * | 2020-12-21 | 2024-01-25 | ２セブンティ バイオ インコーポレイテッド | 部位特異的変異導入のための組成物及び方法 |
| US20250127811A1 (en) | 2021-01-28 | 2025-04-24 | Precision Biosciences, Inc. | Modulation of tgf beta signaling in genetically-modified eukaryotic cells |
| WO2023081756A1 (en) | 2021-11-03 | 2023-05-11 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Precise genome editing using retrons |
| WO2023081767A1 (en) | 2021-11-05 | 2023-05-11 | Precision Biosciences, Inc. | Methods for immunotherapy |
| MX2024006051A (es) | 2021-11-23 | 2024-06-26 | Cellectis Sa | Nuevos andamios de proteinas tale con relaciones de actividad en objetivo/fuera de objetivo mejoradas. |
| WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| EP4646223A1 (en) | 2023-01-05 | 2025-11-12 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for the human t cell receptor alpha constant region gene |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011156430A2 (en) * | 2010-06-07 | 2011-12-15 | Fred Hutchinson Cancer Research Center | Generation and expression of engineered i-onui endonuclease and its homologues and uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8956828B2 (en) * | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| EP3320910A1 (en) * | 2011-04-05 | 2018-05-16 | Cellectis | Method for the generation of compact tale-nucleases and uses thereof |
| WO2013009525A1 (en) * | 2011-07-08 | 2013-01-17 | Cellectis S.A. | Method for increasing the efficiency of double-strand break-induced mutagenssis |
| WO2013068845A2 (en) * | 2011-11-07 | 2013-05-16 | The University Of Western Ontario | Endonuclease for genome editing |
-
2014
- 2014-05-28 AU AU2014273091A patent/AU2014273091B2/en active Active
- 2014-05-28 ES ES14728899T patent/ES2716867T3/es active Active
- 2014-05-28 US US14/891,216 patent/US10000746B2/en active Active
- 2014-05-28 JP JP2016516173A patent/JP6450371B2/ja active Active
- 2014-05-28 EP EP14728899.7A patent/EP3004338B1/en active Active
- 2014-05-28 WO PCT/EP2014/061189 patent/WO2014191527A1/en not_active Ceased
- 2014-05-28 DK DK14728899.7T patent/DK3004338T3/en active
- 2014-05-28 CA CA2913872A patent/CA2913872C/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011156430A2 (en) * | 2010-06-07 | 2011-12-15 | Fred Hutchinson Cancer Research Center | Generation and expression of engineered i-onui endonuclease and its homologues and uses thereof |
Non-Patent Citations (6)
| Title |
|---|
| BAXTER SARAH ET AL, "Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases.", NUCLEIC ACIDS RESEARCH SEP 2012, (2012-09), vol. 40, no. 16, ISSN 1362-4962, pages 7985 - 8000 * |
| HAFEZ MOHAMED ET AL, "Homing endonucleases: DNA scissors on a mission", GENOME, (2012-08), vol. 55, no. 8, pages 553 - 569 * |
| PROVASI ELENA ET AL, "TCR Gene Editing Results in Effective Immunotherapy of Leukemia without the Development of GvHD", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, (2011-12-13), vol. 118, no. 21, ISSN 0006-4971, page 307 * |
| RYO TAKEUCHI ET AL, "Tapping natural reservoirs of homing endonucleases for targeted gene modification", PROC. NAT. ACAD. SCI. 2011, vol. 108, no. 32, pages 13077 - 13082 * |
| S. BOISSEL ET AL, "megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering", NUCLEIC ACIDS RESEARCH, (2013-11-26), vol. 42, no. 4, doi:10.1093/nar/gkt1224, ISSN 0305-1048, pages 2591 - 2601 * |
| TORIKAI H ET AL, "A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR.", BLOOD. 2012, vol. 119, no. 24, pages 5697 - 5705 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6450371B2 (ja) | 2019-01-09 |
| US20160130569A1 (en) | 2016-05-12 |
| HK1223394A1 (en) | 2017-07-28 |
| WO2014191527A1 (en) | 2014-12-04 |
| DK3004338T3 (en) | 2019-04-08 |
| US10000746B2 (en) | 2018-06-19 |
| EP3004338A1 (en) | 2016-04-13 |
| CA2913872C (en) | 2022-01-18 |
| EP3004338B1 (en) | 2019-01-02 |
| CA2913872A1 (en) | 2014-12-04 |
| ES2716867T3 (es) | 2019-06-17 |
| AU2014273091A1 (en) | 2015-12-03 |
| JP2016520320A (ja) | 2016-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2014273091B2 (en) | A LAGLIDADG homing endonuclease cleaving the T cell receptor alpha gene and uses thereof | |
| EP3004149B1 (en) | A laglidadg homing endonuclease cleaving the c-c chemokine receptor type-5 (ccr5) gene and uses thereof | |
| CN102264915B (zh) | 失活谷氨酰胺合成酶基因表达的方法和组合物 | |
| WO2020041249A1 (en) | Engineered target specific base editors | |
| JP2019520844A (ja) | ゲノムｄｎａを改変するための方法および組成物 | |
| CN119490976A (zh) | 改造的cascade组分和cascade复合体 | |
| IL202555A (en) | Mega-nuclease variants for hatching a DNA target sequence from a 26 rosa mouse and their uses | |
| JP7641233B2 (ja) | 改善された遺伝子編集のための組成物及び方法 | |
| US20130189759A1 (en) | Meganucleases variants cleaving a dna target sequence in the nanog gene and uses thereof | |
| JP2024532784A (ja) | 新規なｏｍｎｉ－１１５、１２４、１２７、１４４～１４９、１５９、２１８、２３７、２４８、２５１～２５３及び２５９ｃｒｉｓｐｒヌクレアーゼ | |
| HK1223394B (en) | A laglidadg homing endonuclease cleaving the t cell receptor alpha gene and uses thereof | |
| Jang et al. | Genome editing systems in novel therapies | |
| HK1223373B (en) | A laglidadg homing endonuclease cleaving the c-c chemokine receptor type-5 (ccr5) gene and uses thereof | |
| US20160138047A1 (en) | Improved polynucleotide sequences encoding tale repeats | |
| WO2012007848A2 (en) | Meganuclease variants cleaving a dna target sequence in the was gene and uses thereof | |
| Class et al. | Patent application title: A LAGLIDADG HOMING ENDONUCLEASE CLEAVING THE T CELL RECEPTOR ALPHA GENE AND USES THEREOF Inventors: Jordan Jarjour (Seattle, WA, US) Alexander Astrakhan (Seattle, WA, US) | |
| Checketts | Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |