JP2014530603A - Ｈｉｖ感染を制御するための方法および組成物 - Google Patents
Ｈｉｖ感染を制御するための方法および組成物 Download PDFInfo
- Publication number
- JP2014530603A JP2014530603A JP2014534726A JP2014534726A JP2014530603A JP 2014530603 A JP2014530603 A JP 2014530603A JP 2014534726 A JP2014534726 A JP 2014534726A JP 2014534726 A JP2014534726 A JP 2014534726A JP 2014530603 A JP2014530603 A JP 2014530603A
- Authority
- JP
- Japan
- Prior art keywords
- hiv
- cells
- cell
- gene
- sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 71
- 208000031886 HIV Infections Diseases 0.000 title claims abstract description 8
- 208000037357 HIV infectious disease Diseases 0.000 title claims abstract description 8
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 title claims abstract description 8
- 239000000203 mixture Substances 0.000 title abstract description 31
- 108700019146 Transgenes Proteins 0.000 claims abstract description 71
- 230000036436 anti-hiv Effects 0.000 claims abstract description 40
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims abstract description 37
- 230000010076 replication Effects 0.000 claims abstract description 22
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 208000015181 infectious disease Diseases 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 150
- 108090000623 proteins and genes Proteins 0.000 claims description 141
- 102000004169 proteins and genes Human genes 0.000 claims description 58
- 230000014509 gene expression Effects 0.000 claims description 42
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 37
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 33
- 108020004459 Small interfering RNA Proteins 0.000 claims description 16
- 210000000130 stem cell Anatomy 0.000 claims description 15
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 14
- 101150017501 CCR5 gene Proteins 0.000 claims description 12
- 108010004483 APOBEC-3G Deaminase Proteins 0.000 claims description 11
- 102100038076 DNA dC->dU-editing enzyme APOBEC-3G Human genes 0.000 claims description 11
- 108010083930 HIV Receptors Proteins 0.000 claims description 8
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 7
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 7
- 108091007916 Zinc finger transcription factors Proteins 0.000 claims description 6
- 102000038627 Zinc finger transcription factors Human genes 0.000 claims description 6
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 6
- 230000008685 targeting Effects 0.000 claims description 6
- 101150066398 CXCR4 gene Proteins 0.000 claims description 5
- 206010010144 Completed suicide Diseases 0.000 claims description 5
- 102000006481 HIV Receptors Human genes 0.000 claims description 5
- 108010076039 Polyproteins Proteins 0.000 claims description 5
- 108010088751 Albumins Proteins 0.000 claims description 4
- 108090000994 Catalytic RNA Proteins 0.000 claims description 4
- 102000053642 Catalytic RNA Human genes 0.000 claims description 4
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 claims description 4
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 claims description 4
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 claims description 4
- 108091092562 ribozyme Proteins 0.000 claims description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 3
- 210000004443 dendritic cell Anatomy 0.000 claims description 3
- 210000002540 macrophage Anatomy 0.000 claims description 3
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 claims description 2
- 235000011449 Rosa Nutrition 0.000 claims description 2
- 102000009027 Albumins Human genes 0.000 claims 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 claims 1
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 claims 1
- 101710163270 Nuclease Proteins 0.000 abstract description 60
- 230000005782 double-strand break Effects 0.000 abstract description 9
- 238000003776 cleavage reaction Methods 0.000 description 77
- 230000007017 scission Effects 0.000 description 77
- 239000013598 vector Substances 0.000 description 61
- 150000007523 nucleic acids Chemical class 0.000 description 60
- 102000039446 nucleic acids Human genes 0.000 description 55
- 108020004707 nucleic acids Proteins 0.000 description 55
- 230000004568 DNA-binding Effects 0.000 description 47
- 230000027455 binding Effects 0.000 description 36
- 241000725303 Human immunodeficiency virus Species 0.000 description 33
- 102000040430 polynucleotide Human genes 0.000 description 33
- 108091033319 polynucleotide Proteins 0.000 description 33
- 239000002157 polynucleotide Substances 0.000 description 33
- 108020004414 DNA Proteins 0.000 description 29
- 239000002773 nucleotide Substances 0.000 description 29
- 125000003729 nucleotide group Chemical group 0.000 description 29
- 108090000765 processed proteins & peptides Proteins 0.000 description 26
- 239000004055 small Interfering RNA Substances 0.000 description 26
- 102000004196 processed proteins & peptides Human genes 0.000 description 24
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 23
- 239000011701 zinc Substances 0.000 description 23
- 229910052725 zinc Inorganic materials 0.000 description 23
- 229920001184 polypeptide Polymers 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 21
- 230000010354 integration Effects 0.000 description 20
- 108010077544 Chromatin Proteins 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 18
- 210000003483 chromatin Anatomy 0.000 description 18
- 230000004927 fusion Effects 0.000 description 17
- 230000009368 gene silencing by RNA Effects 0.000 description 17
- 108020001507 fusion proteins Proteins 0.000 description 16
- 102000037865 fusion proteins Human genes 0.000 description 16
- 230000003612 virological effect Effects 0.000 description 16
- 241000702421 Dependoparvovirus Species 0.000 description 15
- 241000700605 Viruses Species 0.000 description 15
- 230000035772 mutation Effects 0.000 description 15
- 239000013603 viral vector Substances 0.000 description 15
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 14
- 108010042407 Endonucleases Proteins 0.000 description 14
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 14
- 238000001415 gene therapy Methods 0.000 description 14
- 230000001413 cellular effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 108091027967 Small hairpin RNA Proteins 0.000 description 11
- 101710185494 Zinc finger protein Proteins 0.000 description 11
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 241000701161 unidentified adenovirus Species 0.000 description 11
- 108091026890 Coding region Proteins 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 108091008146 restriction endonucleases Proteins 0.000 description 10
- 230000001177 retroviral effect Effects 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 9
- 108091023040 Transcription factor Proteins 0.000 description 9
- 102000040945 Transcription factor Human genes 0.000 description 9
- 210000000349 chromosome Anatomy 0.000 description 9
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 8
- 102100031780 Endonuclease Human genes 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 238000002744 homologous recombination Methods 0.000 description 8
- 230000006801 homologous recombination Effects 0.000 description 8
- -1 polymerase Proteins 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000002103 transcriptional effect Effects 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 102100034349 Integrase Human genes 0.000 description 7
- 230000002950 deficient Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 239000002502 liposome Substances 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 6
- 102000004533 Endonucleases Human genes 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 230000002779 inactivation Effects 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 230000007018 DNA scission Effects 0.000 description 5
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 5
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 5
- 241000713666 Lentivirus Species 0.000 description 5
- 241000589634 Xanthomonas Species 0.000 description 5
- 238000009510 drug design Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000010361 transduction Methods 0.000 description 5
- 230000026683 transduction Effects 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 5
- 239000013607 AAV vector Substances 0.000 description 4
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 4
- 101710096438 DNA-binding protein Proteins 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 101710149951 Protein Tat Proteins 0.000 description 4
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 4
- 101710201961 Virion infectivity factor Proteins 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000002759 chromosomal effect Effects 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- 238000010353 genetic engineering Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000001638 lipofection Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010061833 Integrases Proteins 0.000 description 3
- 241000282560 Macaca mulatta Species 0.000 description 3
- 102000011931 Nucleoproteins Human genes 0.000 description 3
- 108010061100 Nucleoproteins Proteins 0.000 description 3
- 108010047956 Nucleosomes Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000010362 genome editing Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000001623 nucleosome Anatomy 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 101000889905 Enterobacteria phage RB3 Intron-associated endonuclease 3 Proteins 0.000 description 2
- 101000889904 Enterobacteria phage T4 Defective intron-associated endonuclease 3 Proteins 0.000 description 2
- 101000889900 Enterobacteria phage T4 Intron-associated endonuclease 1 Proteins 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 241000233866 Fungi 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
- 102000006947 Histones Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 101000742736 Homo sapiens DNA dC->dU-editing enzyme APOBEC-3G Proteins 0.000 description 2
- 101000687346 Homo sapiens PR domain zinc finger protein 2 Proteins 0.000 description 2
- 101000680666 Homo sapiens Tripartite motif-containing protein 5 Proteins 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 206010024305 Leukaemia monocytic Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 102100024885 PR domain zinc finger protein 2 Human genes 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- 101100087805 Ralstonia solanacearum rip19 gene Proteins 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 238000010459 TALEN Methods 0.000 description 2
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 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
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000003995 blood forming stem cell Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000003763 chloroplast Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000000412 dendrimer Substances 0.000 description 2
- 229920000736 dendritic polymer Polymers 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 2
- 229960002963 ganciclovir Drugs 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 102000054962 human APOBEC3G Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000012212 insulator Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 201000006894 monocytic leukemia Diseases 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000006780 non-homologous end joining Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000009437 off-target effect Effects 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 230000003032 phytopathogenic effect Effects 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000021127 protein binding proteins Human genes 0.000 description 2
- 108091011138 protein binding proteins Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108700004030 rev Genes Proteins 0.000 description 2
- 101150098213 rev gene Proteins 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 230000005783 single-strand break Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000010473 stable expression Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000010415 tropism Effects 0.000 description 2
- 238000010396 two-hybrid screening Methods 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- ALNDFFUAQIVVPG-NGJCXOISSA-N (2r,3r,4r)-3,4,5-trihydroxy-2-methoxypentanal Chemical compound CO[C@@H](C=O)[C@H](O)[C@H](O)CO ALNDFFUAQIVVPG-NGJCXOISSA-N 0.000 description 1
- OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 108010013043 Acetylesterase Proteins 0.000 description 1
- 101710159080 Aconitate hydratase A Proteins 0.000 description 1
- 101710159078 Aconitate hydratase B Proteins 0.000 description 1
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 1
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 1
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 1
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000004274 CCR5 Receptors Human genes 0.000 description 1
- 108010017088 CCR5 Receptors Proteins 0.000 description 1
- 108010061299 CXCR4 Receptors Proteins 0.000 description 1
- 102000012000 CXCR4 Receptors Human genes 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 102000005381 Cytidine Deaminase Human genes 0.000 description 1
- 108010031325 Cytidine deaminase Proteins 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101000889899 Enterobacteria phage T4 Intron-associated endonuclease 2 Proteins 0.000 description 1
- 101800001467 Envelope glycoprotein E2 Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 102000048120 Galactokinases Human genes 0.000 description 1
- 108700023157 Galactokinases Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000175212 Herpesvirales Species 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 102100039869 Histone H2B type F-S Human genes 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 1
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
- 101001109800 Homo sapiens Pro-neuregulin-1, membrane-bound isoform Proteins 0.000 description 1
- 108010070875 Human Immunodeficiency Virus tat Gene Products Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 108091036060 Linker DNA Proteins 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 108010059724 Micrococcal Nuclease Proteins 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 108010086093 Mung Bean Nuclease Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 108010008964 Non-Histone Chromosomal Proteins Proteins 0.000 description 1
- 102000006570 Non-Histone Chromosomal Proteins Human genes 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108091007494 Nucleic acid- binding domains Proteins 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 101710105008 RNA-binding protein Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 241000232299 Ralstonia Species 0.000 description 1
- 101100272715 Ralstonia solanacearum (strain GMI1000) brg11 gene Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 101001025539 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Homothallic switching endonuclease Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 101800001271 Surface protein Proteins 0.000 description 1
- 101150003725 TK gene Proteins 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 102100022405 Tripartite motif-containing protein 5 Human genes 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 241000589636 Xanthomonas campestris Species 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000749 co-immunoprecipitation Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 108010050663 endodeoxyribonuclease CreI Proteins 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 102000055650 human NRG1 Human genes 0.000 description 1
- 102000052612 human TRIM5 Human genes 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 244000000003 plant pathogen Species 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 238000003160 two-hybrid assay Methods 0.000 description 1
- 230000024275 uncoating of virus Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
- C07K2319/81—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor containing a Zn-finger domain for DNA binding
-
- 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)
- C12Y301/21—Endodeoxyribonucleases producing 5'-phosphomonoesters (3.1.21)
- C12Y301/21004—Type II site-specific deoxyribonuclease (3.1.21.4)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161544101P | 2011-10-06 | 2011-10-06 | |
| US61/544,101 | 2011-10-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2014530603A true JP2014530603A (ja) | 2014-11-20 |
| JP2014530603A5 JP2014530603A5 (enExample) | 2015-10-08 |
Family
ID=48044158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014534726A Pending JP2014530603A (ja) | 2011-10-06 | 2012-10-04 | Ｈｉｖ感染を制御するための方法および組成物 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20130171732A1 (enExample) |
| EP (1) | EP2764102A4 (enExample) |
| JP (1) | JP2014530603A (enExample) |
| AU (1) | AU2012318562A1 (enExample) |
| CA (1) | CA2849920A1 (enExample) |
| HK (1) | HK1200491A1 (enExample) |
| WO (1) | WO2013052681A1 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6188703B2 (ja) * | 2011-10-27 | 2017-08-30 | サンガモ セラピューティクス， インコーポレイテッド | Ｈｐｒｔ遺伝子座を修飾するための方法および組成物 |
| WO2014093701A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| AU2013359199C1 (en) | 2012-12-12 | 2021-06-17 | Massachusetts Institute Of Technology | Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications |
| ES2701749T3 (es) | 2012-12-12 | 2019-02-25 | Broad Inst Inc | Métodos, modelos, sistemas y aparatos para identificar secuencias diana para enzimas Cas o sistemas CRISPR-Cas para secuencias diana y transmitir resultados de los mismos |
| SG11201510284XA (en) | 2013-06-17 | 2016-01-28 | Broad Inst Inc | Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy |
| AU2014281026B2 (en) | 2013-06-17 | 2020-05-28 | Massachusetts Institute Of Technology | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
| WO2014204725A1 (en) * | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation |
| RU2716421C2 (ru) | 2013-06-17 | 2020-03-11 | Те Брод Инститьют Инк. | Доставка, применение и применения в терапии систем crispr-cas и композиций для целенаправленного воздействия на нарушения и заболевания с использованием вирусных компонентов |
| CA2915845A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute, Inc. | Delivery, engineering and optimization of systems, methods and compositions for targeting and modeling diseases and disorders of post mitotic cells |
| EP3725885A1 (en) | 2013-06-17 | 2020-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| EP3071695A2 (en) * | 2013-11-18 | 2016-09-28 | Crispr Therapeutics AG | Crispr-cas system materials and methods |
| KR20250068794A (ko) | 2013-12-12 | 2025-05-16 | 더 브로드 인스티튜트, 인코퍼레이티드 | 게놈 편집을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 조성물의 전달, 용도 및 치료적 응용 |
| EP3080261B1 (en) | 2013-12-12 | 2019-05-22 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hbv and viral diseases and disorders |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| AU2014362245A1 (en) | 2013-12-12 | 2016-06-16 | Massachusetts Institute Of Technology | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
| WO2015089486A2 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
| EP4219699A1 (en) | 2013-12-12 | 2023-08-02 | The Broad Institute, Inc. | Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation |
| EP3470089A1 (en) | 2013-12-12 | 2019-04-17 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using particle delivery components |
| US9757420B2 (en) | 2014-07-25 | 2017-09-12 | Sangamo Therapeutics, Inc. | Gene editing for HIV gene therapy |
| EP3985115A1 (en) | 2014-12-12 | 2022-04-20 | The Broad Institute, Inc. | Protected guide rnas (pgrnas) |
| CA2970370A1 (en) | 2014-12-24 | 2016-06-30 | Massachusetts Institute Of Technology | Crispr having or associated with destabilization domains |
| US10059940B2 (en) * | 2015-01-27 | 2018-08-28 | Minghong Zhong | Chemically ligated RNAs for CRISPR/Cas9-lgRNA complexes as antiviral therapeutic agents |
| MX392008B (es) | 2015-06-18 | 2025-03-21 | Broad Inst Inc | Mutaciones de la enzima crispr que reducen los efectos fuera del blanco |
| WO2016205759A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502170A (ja) * | 2005-07-26 | 2009-01-29 | サンガモ バイオサイエンシズ インコーポレイテッド | 外来核酸配列の標的化された組込み及び発現 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1352960A1 (en) * | 2002-04-12 | 2003-10-15 | Viruvation B.V. | Antiviral therapy on the basis of RNA interference |
| WO2007014181A2 (en) * | 2005-07-25 | 2007-02-01 | Johns Hopkins University | Site-specific modification of the human genome using custom-designed zinc finger nucleases |
| US20080003681A1 (en) * | 2006-06-28 | 2008-01-03 | Mahalaxmi Gita Bangera | Methods for altering cellular susceptibility to infection |
| US8563314B2 (en) * | 2007-09-27 | 2013-10-22 | Sangamo Biosciences, Inc. | Methods and compositions for modulating PD1 |
| US8193161B2 (en) * | 2008-06-09 | 2012-06-05 | New York Medical College | Compositions comprising cardiac stem cells overexpressing specific micrornas and methods of their use in repairing damaged myocardium |
| EP2408921B1 (en) * | 2009-03-20 | 2017-04-19 | Sangamo BioSciences, Inc. | Modification of cxcr4 using engineered zinc finger proteins |
| DK2462230T3 (en) * | 2009-08-03 | 2015-10-19 | Recombinetics Inc | METHODS AND COMPOSITIONS FOR TARGETED RE-MODIFICATION |
| CN102071219B (zh) * | 2010-11-05 | 2014-03-12 | 冯小荣 | 改腺载体及其在艾滋病预防和治疗药物中的应用 |
-
2012
- 2012-10-04 AU AU2012318562A patent/AU2012318562A1/en not_active Abandoned
- 2012-10-04 WO PCT/US2012/058775 patent/WO2013052681A1/en not_active Ceased
- 2012-10-04 CA CA 2849920 patent/CA2849920A1/en not_active Abandoned
- 2012-10-04 HK HK15101108.0A patent/HK1200491A1/xx unknown
- 2012-10-04 US US13/645,175 patent/US20130171732A1/en not_active Abandoned
- 2012-10-04 EP EP12838704.0A patent/EP2764102A4/en not_active Withdrawn
- 2012-10-04 JP JP2014534726A patent/JP2014530603A/ja active Pending
-
2015
- 2015-05-28 US US14/724,250 patent/US20150267223A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502170A (ja) * | 2005-07-26 | 2009-01-29 | サンガモ バイオサイエンシズ インコーポレイテッド | 外来核酸配列の標的化された組込み及び発現 |
Non-Patent Citations (3)
| Title |
|---|
| JPN6016020895; Ｎａｔ． Ｂｉｏｔｅｃｈｎｏｌ． Ｖｏｌ． ２８， ｎｏ． ８, 2010, ｐ． ８３９-８４７ * |
| JPN6016020897; Ｍｏｌ． Ｔｈｅｒ． Ｖｏｌ． １２， Ｎｏ． ５, 2005, ｐ． ９００-９０９ * |
| JPN6016020900; Ｎａｔ． Ｍｅｔｈｏｄｓ Ｖｏｌ． ８， Ｎｏ． １０, 20110821, ｐ． ８６１-８６９ * |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1200491A1 (en) | 2015-08-07 |
| WO2013052681A1 (en) | 2013-04-11 |
| CA2849920A1 (en) | 2013-04-11 |
| EP2764102A1 (en) | 2014-08-13 |
| EP2764102A4 (en) | 2015-06-10 |
| US20150267223A1 (en) | 2015-09-24 |
| AU2012318562A1 (en) | 2014-04-10 |
| US20130171732A1 (en) | 2013-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230203540A1 (en) | Methods and compositions for nuclease-mediated targeted integration of transgenes into mammalian liver cells | |
| JP7218401B2 (ja) | リソソーム貯蔵疾患の処置のための方法および組成物 | |
| JP6875362B2 (ja) | ヌクレアーゼ媒介ゲノム遺伝子操作のための送達方法および組成物 | |
| JP6629917B2 (ja) | 遺伝子疾患の治療のための方法および組成物 | |
| JP2014530603A (ja) | Ｈｉｖ感染を制御するための方法および組成物 | |
| US9833479B2 (en) | Gene correction of SCID-related genes in hematopoietic stem and progenitor cells | |
| JP6188703B2 (ja) | Ｈｐｒｔ遺伝子座を修飾するための方法および組成物 | |
| JP7042263B2 (ja) | ファブリー病の治療のための方法および組成物 | |
| JP2019193679A (ja) | 造血幹細胞におけるヌクレアーゼ媒介性ゲノム工学および補正のための方法および組成物 | |
| JP2021536229A (ja) | 操作された標的特異的な塩基エディター | |
| JP2022105621A (ja) | 造血幹細胞および前駆細胞におけるｓｃｉｄ関連遺伝子の遺伝子修正 | |
| JP2020518245A (ja) | 嚢胞性線維症膜貫通コンダクタンス制御因子（ｃｆｔｒ）遺伝子の改変のための方法および組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150821 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150821 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160602 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20161228 |