CN104560999B - 抑制ADAMTS‑5基因的siRNA及其应用 - Google Patents
抑制ADAMTS‑5基因的siRNA及其应用 Download PDFInfo
- Publication number
- CN104560999B CN104560999B CN201410828587.5A CN201410828587A CN104560999B CN 104560999 B CN104560999 B CN 104560999B CN 201410828587 A CN201410828587 A CN 201410828587A CN 104560999 B CN104560999 B CN 104560999B
- Authority
- CN
- China
- Prior art keywords
- sirna
- double
- stranded
- modification
- 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
- 108020004459 Small interfering RNA Proteins 0.000 title claims abstract description 271
- 108091005663 ADAMTS5 Proteins 0.000 title abstract description 45
- 108090000623 proteins and genes Proteins 0.000 title abstract description 45
- 102000051389 ADAMTS5 Human genes 0.000 title abstract description 24
- 238000007385 chemical modification Methods 0.000 claims abstract description 48
- 206010061218 Inflammation Diseases 0.000 claims abstract description 28
- 230000004054 inflammatory process Effects 0.000 claims abstract description 28
- 230000000295 complement effect Effects 0.000 claims abstract description 22
- 206010003246 arthritis Diseases 0.000 claims abstract description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 120
- 238000012986 modification Methods 0.000 claims description 68
- 230000004048 modification Effects 0.000 claims description 66
- 230000000692 anti-sense effect Effects 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 32
- 210000000845 cartilage Anatomy 0.000 claims description 28
- 102000039446 nucleic acids Human genes 0.000 claims description 26
- 108020004707 nucleic acids Proteins 0.000 claims description 26
- 150000007523 nucleic acids Chemical class 0.000 claims description 26
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 claims description 25
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 18
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 18
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 17
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 16
- 201000008482 osteoarthritis Diseases 0.000 claims description 15
- 239000005547 deoxyribonucleotide Substances 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 206010016654 Fibrosis Diseases 0.000 claims description 10
- 239000002773 nucleotide Substances 0.000 claims description 10
- 125000003729 nucleotide group Chemical group 0.000 claims description 10
- 108091028664 Ribonucleotide Proteins 0.000 claims description 9
- 230000004761 fibrosis Effects 0.000 claims description 9
- 235000012000 cholesterol Nutrition 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 239000002336 ribonucleotide Substances 0.000 claims description 8
- 150000002475 indoles Chemical class 0.000 claims description 7
- 229930024421 Adenine Natural products 0.000 claims description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 6
- 229960000643 adenine Drugs 0.000 claims description 6
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 6
- 229940035893 uracil Drugs 0.000 claims description 6
- 210000001258 synovial membrane Anatomy 0.000 claims description 5
- 230000003628 erosive effect Effects 0.000 claims description 4
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229930182830 galactose Natural products 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 201000004595 synovitis Diseases 0.000 claims description 3
- 229940113082 thymine Drugs 0.000 claims description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 claims description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 5
- 230000014509 gene expression Effects 0.000 abstract description 58
- 230000002757 inflammatory effect Effects 0.000 abstract description 31
- 230000001629 suppression Effects 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 8
- 210000000988 bone and bone Anatomy 0.000 abstract description 7
- 238000002347 injection Methods 0.000 abstract description 5
- 239000007924 injection Substances 0.000 abstract description 5
- 102000004127 Cytokines Human genes 0.000 abstract description 4
- 108090000695 Cytokines Proteins 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 92
- 241000700159 Rattus Species 0.000 description 48
- 108020004414 DNA Proteins 0.000 description 37
- 108091007505 ADAM17 Proteins 0.000 description 36
- 239000013642 negative control Substances 0.000 description 32
- 238000000034 method Methods 0.000 description 30
- 239000000047 product Substances 0.000 description 29
- CVYPRDPBCXSVBN-WDZFZDKYSA-N (5z)-5-[[5-[(4-chlorophenyl)methylsulfanyl]-1-methyl-3-(trifluoromethyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound C=1C=C(Cl)C=CC=1CSC=1N(C)N=C(C(F)(F)F)C=1\C=C1/SC(=S)NC1=O CVYPRDPBCXSVBN-WDZFZDKYSA-N 0.000 description 28
- 238000002474 experimental method Methods 0.000 description 28
- 102000043279 ADAM17 Human genes 0.000 description 26
- 108020004999 messenger RNA Proteins 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 108090000193 Interleukin-1 beta Proteins 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 17
- 238000001514 detection method Methods 0.000 description 16
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 14
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 14
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 14
- 102100040247 Tumor necrosis factor Human genes 0.000 description 14
- 239000002299 complementary DNA Substances 0.000 description 14
- 102000003777 Interleukin-1 beta Human genes 0.000 description 13
- 239000010410 layer Substances 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 239000012097 Lipofectamine 2000 Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 101150056050 ADAM17 gene Proteins 0.000 description 9
- 230000030279 gene silencing Effects 0.000 description 9
- 102000053602 DNA Human genes 0.000 description 8
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- 102000000589 Interleukin-1 Human genes 0.000 description 8
- 108010002352 Interleukin-1 Proteins 0.000 description 8
- 238000001962 electrophoresis Methods 0.000 description 8
- 230000005499 meniscus Effects 0.000 description 8
- 102100036601 Aggrecan core protein Human genes 0.000 description 7
- 108010067219 Aggrecans Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 230000001575 pathological effect Effects 0.000 description 7
- 150000003013 phosphoric acid derivatives Chemical group 0.000 description 7
- 238000010839 reverse transcription Methods 0.000 description 7
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 102000000503 Collagen Type II Human genes 0.000 description 6
- 108010041390 Collagen Type II Proteins 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 239000003292 glue Substances 0.000 description 6
- 210000000629 knee joint Anatomy 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 102000005741 Metalloproteases Human genes 0.000 description 5
- 108010006035 Metalloproteases Proteins 0.000 description 5
- 210000003321 cartilage cell Anatomy 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- 238000012226 gene silencing method Methods 0.000 description 5
- 210000002414 leg Anatomy 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 229950003937 tolonium Drugs 0.000 description 5
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 5
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 4
- 229920001661 Chitosan Polymers 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 108010087230 Sincalide Proteins 0.000 description 4
- 102000002938 Thrombospondin Human genes 0.000 description 4
- 108060008245 Thrombospondin Proteins 0.000 description 4
- 230000002917 arthritic effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000010609 cell counting kit-8 assay Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000012160 loading buffer Substances 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102000029791 ADAM Human genes 0.000 description 3
- 108091022885 ADAM Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 3
- 101000801228 Homo sapiens Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 3
- 238000011530 RNeasy Mini Kit Methods 0.000 description 3
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 3
- 108010003059 aggrecanase Proteins 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000004043 dyeing Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 206010020718 hyperplasia Diseases 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000004570 mortar (masonry) Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 101150096316 5 gene Proteins 0.000 description 2
- 102000029750 ADAMTS Human genes 0.000 description 2
- 108091022879 ADAMTS Proteins 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010019160 Pancreatin Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 102100036034 Thrombospondin-1 Human genes 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000002308 calcification Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000012930 cell culture fluid Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 238000001215 fluorescent labelling Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- -1 methoxyl group Chemical group 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 231100001083 no cytotoxicity Toxicity 0.000 description 2
- 229940055695 pancreatin Drugs 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000007119 pathological manifestation Effects 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 201000003068 rheumatic fever Diseases 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 230000006807 siRNA silencing Effects 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 1
- 101800000620 Disintegrin-like Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 101000835893 Homo sapiens Mothers against decapentaplegic homolog 4 Proteins 0.000 description 1
- 101000659879 Homo sapiens Thrombospondin-1 Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 1
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 108010047320 Pepsinogen A Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 101150033527 TNF gene Proteins 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 101150009602 mesh gene Proteins 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 108010048734 sclerotin Proteins 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000005065 subchondral bone plate Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 108010088577 zinc-binding protein Proteins 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3235—Chemical structure of the sugar modified ring structure having the O of the ribose replaced by another atom
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/334—Modified C
- C12N2310/3341—5-Methylcytosine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/335—Modified T or U
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3513—Protein; Peptide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3517—Marker; Tag
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (11)
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201711239584.8A CN107904239B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS-5基因的siRNA及其应用 |
CN201410828587.5A CN104560999B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS‑5基因的siRNA及其应用 |
ES15872041T ES2833028T3 (es) | 2014-12-25 | 2015-12-23 | Composiciones y métodos para inhibir la expresión de ADAMTS-5 y ADAM17 |
JP2017552533A JP6706628B2 (ja) | 2014-12-25 | 2015-12-23 | Adamts−5又はadam17発現を抑制する組成物及びその方法 |
US15/539,671 US10709729B2 (en) | 2014-12-25 | 2015-12-23 | Compositions and methods for inhibiting expression of ADAMTS-5 and ADAM17 |
EP15872041.7A EP3237619B8 (en) | 2014-12-25 | 2015-12-23 | Compositions and methods for inhibiting expression of adamts-5 and adam17 |
DK15872041.7T DK3237619T3 (da) | 2014-12-25 | 2015-12-23 | Sammensætninger og fremgangsmåder til at inhibere ekspression af adamts-5 og adam17 |
PCT/IB2015/002574 WO2016103042A1 (en) | 2014-12-25 | 2015-12-23 | Compositions and methods for inhibiting expression of adamts-5 and adam17 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410828587.5A CN104560999B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS‑5基因的siRNA及其应用 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201711239584.8A Division CN107904239B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS-5基因的siRNA及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104560999A CN104560999A (zh) | 2015-04-29 |
CN104560999B true CN104560999B (zh) | 2018-01-09 |
Family
ID=53078078
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201711239584.8A Active CN107904239B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS-5基因的siRNA及其应用 |
CN201410828587.5A Active CN104560999B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS‑5基因的siRNA及其应用 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201711239584.8A Active CN107904239B (zh) | 2014-12-25 | 2014-12-25 | 抑制ADAMTS-5基因的siRNA及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (2) | CN107904239B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK3237619T3 (da) | 2014-12-25 | 2020-11-09 | Guangzhou Ribobio Co Ltd | Sammensætninger og fremgangsmåder til at inhibere ekspression af adamts-5 og adam17 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2413804T3 (es) * | 2006-05-19 | 2013-07-17 | Alcon Research, Ltd. | Inhibición mediada por ARNi de estados relacionados con factor de necrosis tumoral-alfa |
CL2008002277A1 (es) * | 2007-08-03 | 2009-07-17 | Alcon Res Ltd | Metodo para tratar un trastorno ocular relacionado con tnf alfa que comprende una molecula de arn interferente que actua en la expresion del arnm de tnfr1 o tace mediante interferencia de arn; molecula de arn interferente; composicion que comprende dicho interferente. |
EP2367418A4 (en) * | 2008-11-25 | 2012-04-18 | Univ Rochester | ANIMAL MODEL FOR OSTEOARTHRITIS AND BAND DISEASE |
-
2014
- 2014-12-25 CN CN201711239584.8A patent/CN107904239B/zh active Active
- 2014-12-25 CN CN201410828587.5A patent/CN104560999B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN104560999A (zh) | 2015-04-29 |
CN107904239B (zh) | 2020-11-27 |
CN107904239A (zh) | 2018-04-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kleinberger et al. | Mechanisms of granulin deficiency: lessons from cellular and animal models | |
CN105960459A (zh) | 抑制neat1用于治疗实体肿瘤 | |
KR20150129726A (ko) | 연조직 회복 및 재생을 위한 세포 재배치된 콜라겐 매트릭스 | |
Geng et al. | Association of TNF‐α with Impaired Migration Capacity of Mesenchymal Stem Cells in Patients with Systemic Lupus Erythematosus | |
JP7080516B2 (ja) | 軟骨細胞の肥大分化を抑制する薬物の製造又は遺伝子デリバリーシステムにおけるLncRNA-32598の応用 | |
CN111789835A (zh) | 一种抗动脉粥样硬化炎症的药物、抗炎作用检测方法 | |
CN104560997B (zh) | 抑制ADAMTS-5和ADAM17基因的siRNA组合物及其应用 | |
Chen et al. | The mechanisms of β-catenin on keloid fibroblast cells proliferation and apoptosis. | |
Zhang et al. | Transplantation of olfactory ensheathing cells combined with chitosan down-regulates the expression of P2X7 receptor in the spinal cord and inhibits neuropathic pain | |
CN104560999B (zh) | 抑制ADAMTS‑5基因的siRNA及其应用 | |
CN107028970A (zh) | miR‑1288在诊断或治疗骨关节炎疾病中的应用 | |
Meng et al. | Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling | |
CN104561000B (zh) | 抑制cd44基因的寡聚核酸及其应用 | |
CN107982536A (zh) | 一种药物作用靶点的组合物和应用 | |
CN101843632B (zh) | miR-145在制备治疗炎症药物中的应用 | |
CN104498498A (zh) | 抑制ADAM17基因的siRNA及其应用 | |
CN107106706A (zh) | lmo4基因表达的抑制剂在制备银屑病外用型治疗药物中的用途 | |
CN101955975A (zh) | 组织金属蛋白酶抑制因子siRNA表达载体的构建及肝硬化治疗应用 | |
Ying et al. | Fermitin family homolog 2 (Kindlin-2) affects vascularization during the wound healing process by regulating the Wnt/β-catenin signaling pathway in vascular endothelial cells | |
Duan et al. | Mesenchymal stem cell exosomes inhibit nucleus pulposus cell apoptosis via the miR-125b-5p/TRAF6/NF-κB pathway axis: Exosomes attenuate disc degeneration through the miR-125b/TRAF6/NF-κB axis | |
CN107523566A (zh) | 一种mcm3ap‑as1基因的靶向抑制剂及其用途 | |
Yao et al. | Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy | |
CN104450710B (zh) | 抑制myd88基因的寡聚核酸及其应用 | |
Wang et al. | Tetrahedral Framework Nucleic Acid Loaded miR‐23b Inhibits Synovial Inflammation and Cartilage Matrix Degradation in the Treatment of Rheumatoid Arthritis | |
CN104436195B (zh) | miR-155在制备防治急性肺损伤药物中的用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20200917 Address after: 510663 unit 1302, 1303, unit C3 of innovation mansion, No. 182, science Avenue, science Avenue, Guangzhou high tech Industrial Development Zone, Guangdong Province Patentee after: GUANGZHOU RIBOBIO Co.,Ltd. Address before: 510663, C3 building, building 182, science Avenue, 13 Science Avenue, Science Town, Guangzhou, Guangdong Patentee before: GUANGZHOU RIBOBIO Co.,Ltd. Patentee before: GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH, CHINESE ACADEMY OF SCIENCES |
|
TR01 | Transfer of patent right | ||
CP02 | Change in the address of a patent holder | ||
CP02 | Change in the address of a patent holder |
Address after: No.7, tungda street, Science City, Huangpu District, Guangzhou City, Guangdong Province Patentee after: GUANGZHOU RIBOBIO Co.,Ltd. Address before: 510663 unit 1302, 1303, unit C3 of innovation mansion, No. 182, science Avenue, science Avenue, Guangzhou high tech Industrial Development Zone, Guangdong Province Patentee before: GUANGZHOU RIBOBIO Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20210429 Address after: No.7, tungda street, Science City, Huangpu District, Guangzhou City, Guangdong Province Patentee after: GUANGZHOU RIBOBIO Co.,Ltd. Patentee after: Agna biopharmaceutical Co.,Ltd. Address before: No.7, tungda street, Science City, Huangpu District, Guangzhou City, Guangdong Province Patentee before: GUANGZHOU RIBOBIO Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20211124 Address after: 510530 unit 101, building B, No.7, Houda street, Huangpu District, Guangzhou City, Guangdong Province Patentee after: Agna biopharmaceutical Co.,Ltd. Address before: 510530 No.7, tungda street, Science City, Huangpu District, Guangzhou City, Guangdong Province Patentee before: GUANGZHOU RIBOBIO Co.,Ltd. Patentee before: Agna biopharmaceutical Co., Ltd |