NO334573B1 - RNA molekyler som formidler degradering eller blokkering av translasjon av mRNA som koder for klusterin, farmasøytisk sammensetning inneholdende denne samt anvendelse - Google Patents
RNA molekyler som formidler degradering eller blokkering av translasjon av mRNA som koder for klusterin, farmasøytisk sammensetning inneholdende denne samt anvendelse Download PDFInfo
- Publication number
- NO334573B1 NO334573B1 NO20051423A NO20051423A NO334573B1 NO 334573 B1 NO334573 B1 NO 334573B1 NO 20051423 A NO20051423 A NO 20051423A NO 20051423 A NO20051423 A NO 20051423A NO 334573 B1 NO334573 B1 NO 334573B1
- Authority
- NO
- Norway
- Prior art keywords
- cells
- cancer
- rna
- clu
- treatment
- Prior art date
Links
- 108091032973 (ribonucleotides)n+m Proteins 0.000 title claims abstract description 81
- 102000003780 Clusterin Human genes 0.000 title claims description 62
- 108090000197 Clusterin Proteins 0.000 title claims description 62
- 108020004999 messenger RNA Proteins 0.000 title claims description 31
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 230000015556 catabolic process Effects 0.000 title claims description 5
- 238000006731 degradation reaction Methods 0.000 title claims description 5
- 238000013519 translation Methods 0.000 title claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 26
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 15
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 15
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 11
- 201000005202 lung cancer Diseases 0.000 claims abstract description 11
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 11
- 201000001441 melanoma Diseases 0.000 claims abstract description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 9
- 208000006265 Renal cell carcinoma Diseases 0.000 claims abstract description 9
- 206010005003 Bladder cancer Diseases 0.000 claims abstract description 8
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims abstract description 8
- 201000005112 urinary bladder cancer Diseases 0.000 claims abstract description 8
- 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 7
- 201000008968 osteosarcoma Diseases 0.000 claims abstract description 7
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 6
- 206010039491 Sarcoma Diseases 0.000 claims abstract description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 6
- 201000011510 cancer Diseases 0.000 claims description 12
- 230000000295 complement effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 2
- 206010023774 Large cell lung cancer Diseases 0.000 claims 1
- 229940102223 injectable solution Drugs 0.000 claims 1
- 201000009546 lung large cell carcinoma Diseases 0.000 claims 1
- 230000009368 gene silencing by RNA Effects 0.000 abstract description 33
- 108091030071 RNAI Proteins 0.000 abstract description 31
- 230000000694 effects Effects 0.000 abstract description 22
- 102000004371 Insulin-like growth factor binding protein 5 Human genes 0.000 abstract description 20
- 108090000961 Insulin-like growth factor binding protein 5 Proteins 0.000 abstract description 20
- 102000004372 Insulin-like growth factor binding protein 2 Human genes 0.000 abstract description 16
- 108090000964 Insulin-like growth factor binding protein 2 Proteins 0.000 abstract description 16
- 239000003814 drug Substances 0.000 abstract description 9
- 101150087532 mitF gene Proteins 0.000 abstract description 9
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 7
- 101100381978 Mus musculus Braf gene Proteins 0.000 abstract description 6
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 abstract description 5
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 156
- 108090000623 proteins and genes Proteins 0.000 description 30
- 108091034117 Oligonucleotide Proteins 0.000 description 28
- 238000003197 gene knockdown Methods 0.000 description 28
- 230000009467 reduction Effects 0.000 description 27
- 230000006907 apoptotic process Effects 0.000 description 26
- 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 25
- 230000014509 gene expression Effects 0.000 description 25
- 102000004169 proteins and genes Human genes 0.000 description 24
- 239000002609 medium Substances 0.000 description 19
- 238000001890 transfection Methods 0.000 description 15
- 239000002773 nucleotide Substances 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 101150039781 CLU gene Proteins 0.000 description 11
- 238000003757 reverse transcription PCR Methods 0.000 description 11
- 241000894007 species Species 0.000 description 11
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 10
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 10
- 229930012538 Paclitaxel Natural products 0.000 description 10
- 239000002246 antineoplastic agent Substances 0.000 description 10
- 230000030279 gene silencing Effects 0.000 description 10
- 229960001592 paclitaxel Drugs 0.000 description 10
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 10
- 238000000636 Northern blotting Methods 0.000 description 9
- 229940127089 cytotoxic agent Drugs 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 230000000692 anti-sense effect Effects 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 7
- 230000003833 cell viability Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 7
- 239000005556 hormone Substances 0.000 description 7
- 229940088597 hormone Drugs 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 210000000481 breast Anatomy 0.000 description 6
- 238000000326 densiometry Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000010606 normalization Methods 0.000 description 6
- 210000002307 prostate Anatomy 0.000 description 6
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 5
- 206010070834 Sensitisation Diseases 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000008313 sensitization Effects 0.000 description 5
- 230000002269 spontaneous effect Effects 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 230000006820 DNA synthesis Effects 0.000 description 4
- 239000003098 androgen Substances 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 238000012226 gene silencing method Methods 0.000 description 4
- 230000009036 growth inhibition Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000036542 oxidative stress Effects 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 241000282412 Homo Species 0.000 description 3
- 101000942697 Homo sapiens Clusterin Proteins 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 231100000024 genotoxic Toxicity 0.000 description 3
- 230000001738 genotoxic effect Effects 0.000 description 3
- 102000056179 human CLU Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 206010005949 Bone cancer Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 206010053759 Growth retardation Diseases 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 102000003970 Vinculin Human genes 0.000 description 2
- 108090000384 Vinculin Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000009643 clonogenic assay Methods 0.000 description 2
- 231100000096 clonogenic assay Toxicity 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 230000001085 cytostatic effect Effects 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 210000005267 prostate cell Anatomy 0.000 description 2
- 208000023958 prostate neoplasm Diseases 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000005971 DNA damage repair Effects 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
- 101000998774 Homo sapiens Insulin-like peptide INSL5 Proteins 0.000 description 1
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 1
- 102100033266 Insulin-like peptide INSL5 Human genes 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 102100036976 X-ray repair cross-complementing protein 6 Human genes 0.000 description 1
- 101710124907 X-ray repair cross-complementing protein 6 Proteins 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000004715 cellular signal transduction Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000035572 chemosensitivity Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000025915 regulation of apoptotic process Effects 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000003827 upregulation Effects 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
-
- 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
- A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2310/32—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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40519302P | 2002-08-21 | 2002-08-21 | |
| US40815202P | 2002-09-03 | 2002-09-03 | |
| US47238703P | 2003-05-20 | 2003-05-20 | |
| PCT/CA2003/001277 WO2004018676A2 (en) | 2002-08-21 | 2003-08-21 | Rnai probes targeting cancer-related proteins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20051423L NO20051423L (no) | 2005-05-20 |
| NO334573B1 true NO334573B1 (no) | 2014-04-14 |
Family
ID=31950539
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20051423A NO334573B1 (no) | 2002-08-21 | 2005-03-17 | RNA molekyler som formidler degradering eller blokkering av translasjon av mRNA som koder for klusterin, farmasøytisk sammensetning inneholdende denne samt anvendelse |
| NO20121038A NO337130B1 (no) | 2002-08-21 | 2012-09-14 | RNAi-prober som målsøker cancer-relaterte proteiner, farmasøytisk sammensetning inneholdende disse og anvendelse derav |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20121038A NO337130B1 (no) | 2002-08-21 | 2012-09-14 | RNAi-prober som målsøker cancer-relaterte proteiner, farmasøytisk sammensetning inneholdende disse og anvendelse derav |
Country Status (10)
| Country | Link |
|---|---|
| US (5) | US8252918B2 (https=) |
| EP (2) | EP2263679B1 (https=) |
| JP (4) | JP4717633B2 (https=) |
| KR (3) | KR101238701B1 (https=) |
| AU (1) | AU2003258426B2 (https=) |
| CA (2) | CA2494766C (https=) |
| IL (3) | IL166658A (https=) |
| NO (2) | NO334573B1 (https=) |
| NZ (1) | NZ552872A (https=) |
| WO (1) | WO2004018676A2 (https=) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4785252B2 (ja) | 1999-02-26 | 2011-10-05 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | Ｔｒｐｍ−２アンチセンス療法 |
| US7569551B2 (en) | 2000-02-25 | 2009-08-04 | The University Of British Columbia | Chemo- and radiation-sensitization of cancer by antisense TRPM-2 oligodeoxynucleotides |
| WO2003062421A1 (en) * | 2002-01-17 | 2003-07-31 | The University Of British Columbia | Bispecific antisense olignucleotides that inhibit igfbp-2 and igfbp-5 and methods of using same |
| SI1530636T1 (sl) | 2002-08-21 | 2010-12-31 | Stry Liaison Ofiice The University Of British Columbia Umiversity Indu | Zdravljenje melanoma z zniĹľanjem nivojev klusterina |
| KR101238701B1 (ko) * | 2002-08-21 | 2013-03-05 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 암-관련 단백질을 표적으로 하는 알엔에이아이 프로브 |
| US7635673B2 (en) | 2003-03-25 | 2009-12-22 | The Board Of Trustees Of The University Of Illinois | Methods of inhibiting tumor cell proliferation |
| US20040220131A1 (en) * | 2003-04-18 | 2004-11-04 | The University Of British Columbia | Method for treatment of cancerous angiogenic disorders |
| US20050019918A1 (en) * | 2003-06-03 | 2005-01-27 | Hidetoshi Sumimoto | Treatment of cancer by inhibiting BRAF expression |
| JP2005013221A (ja) * | 2003-06-03 | 2005-01-20 | Keio Gijuku | Ｂｒａｆ発現抑制を利用した癌の治療 |
| BRPI0508970A (pt) * | 2004-03-19 | 2007-08-21 | Penn State Res Found | método combinatórios e composições para o tratamento de melanoma |
| US8710020B2 (en) | 2004-04-02 | 2014-04-29 | The University Of British Columbia | Clusterin antisense therapy for treatment of cancer |
| ATE501252T1 (de) * | 2004-06-22 | 2011-03-15 | Univ Illinois | Verfahren zur inhibierung von tumorzellwachstum mit foxm1 sirns |
| WO2006012522A1 (en) * | 2004-07-23 | 2006-02-02 | Pacific Edge Biotechnology Ltd. | Urine markers for detection of bladder cancer |
| WO2006035432A2 (en) * | 2004-09-27 | 2006-04-06 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | Gene silencing for use in dermatology |
| CA2584646C (en) * | 2004-11-23 | 2015-11-03 | The University Of British Columbia | Treatment of cancer with a combination of an agent that perturbs the egf signaling pathway and an oligonucleotide that reduces clusterin levels |
| ES2543341T3 (es) | 2005-09-13 | 2015-08-18 | National Research Council Of Canada | Métodos y composiciones para modular la actividad de células tumorales |
| US8029980B2 (en) | 2006-09-29 | 2011-10-04 | The Board Of Trustees Of The University Of Illinois | Identification and use of agents that modulate oncogenic transcription agent activity |
| WO2008088836A2 (en) * | 2007-01-16 | 2008-07-24 | The Burnham Institute For Medical Research | Compositions and methods for treatment of colorectal cancer |
| WO2008094516A2 (en) | 2007-01-29 | 2008-08-07 | City Of Hope | Multi-targeting short interfering rnas |
| CA2679757A1 (en) * | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting erbb family gene expression and uses thereof |
| US8217161B2 (en) * | 2008-04-22 | 2012-07-10 | Clemson University Research Foundation | Methods of inhibiting multiple cytochrome P450 genes with siRNA |
| EA034462B1 (ru) | 2009-11-24 | 2020-02-11 | Алетиа Байотерапьютикс Инк. | Антикластериновые антитела и антигенсвязывающие фрагменты и их использование для уменьшения объема новообразований |
| EP2673363B1 (en) | 2011-02-11 | 2017-08-23 | The Rockefeller University | Treatment of angiogenesis disorders |
| US9822170B2 (en) | 2012-02-22 | 2017-11-21 | Alethia Biotherapeutics Inc. | Co-use of a clusterin inhibitor with an EGFR inhibitor to treat cancer |
| CA2844640A1 (en) | 2013-12-06 | 2015-06-06 | The University Of British Columbia | Method for treatment of castration-resistant prostate cancer |
| CN106282185B (zh) * | 2016-08-18 | 2020-06-26 | 广州市锐博生物科技有限公司 | 一种用于抑制簇集蛋白基因表达的成套siRNA及其应用 |
| WO2024214933A1 (ko) * | 2023-04-13 | 2024-10-17 | 한양대학교 에리카산학협력단 | 인산화된 igfbp5의 과도한 생성을 차단하여 암을 예방 또는 치료하는 방법 |
| KR102923964B1 (ko) | 2023-04-13 | 2026-02-09 | 한양대학교 에리카산학협력단 | Igfbp5 돌연변이체 또는 이를 발현하는 벡터를 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물 |
| WO2025041340A1 (ja) * | 2023-08-24 | 2025-02-27 | 株式会社Dti | 二重特異性核酸 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5736580A (en) * | 1980-08-13 | 1982-02-27 | Hitachi Ltd | Protecting method for converter |
| CA2108144A1 (en) * | 1991-03-06 | 1992-09-07 | Jack A. Roth | Methods and compositions for the selective inhibition of gene expression |
| AUPM672594A0 (en) * | 1994-07-08 | 1994-08-04 | Royal Children's Hospital Research Foundation | A method for the prophylaxis and/or treatment of proliferative and/or inflammatory skin disorders |
| US20020086386A1 (en) * | 1997-03-04 | 2002-07-04 | Kamb Carl Alexander | B-catenin assays, and compositions therefrom |
| US6383808B1 (en) * | 2000-09-11 | 2002-05-07 | Isis Pharmaceuticals, Inc. | Antisense inhibition of clusterin expression |
| JP4785252B2 (ja) | 1999-02-26 | 2011-10-05 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | Ｔｒｐｍ−２アンチセンス療法 |
| WO2000069454A1 (en) | 1999-05-17 | 2000-11-23 | Board Of Regents, The University Of Texas System | Suppression of endogenous igfbp-2 to inhibit cancer |
| CA2375467C (en) | 1999-07-19 | 2013-10-29 | The University Of British Columbia | Antisense therapy for hormone-regulated tumors |
| US6140126A (en) * | 1999-10-26 | 2000-10-31 | Isis Pharmaceuticals Inc. | Antisense modulation of Y-box binding protein 1 expression |
| GB9927444D0 (en) * | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| US7569551B2 (en) | 2000-02-25 | 2009-08-04 | The University Of British Columbia | Chemo- and radiation-sensitization of cancer by antisense TRPM-2 oligodeoxynucleotides |
| EP1272630A2 (en) * | 2000-03-16 | 2003-01-08 | Genetica, Inc. | Methods and compositions for rna interference |
| ES2336887T5 (es) | 2000-03-30 | 2019-03-06 | Whitehead Inst Biomedical Res | Mediadores de interferencia por ARN específicos de secuencias de ARN |
| EP1317470B1 (en) * | 2000-09-14 | 2011-04-27 | The University Of British Columbia | Antisense insulin-like growth factor binding protein (igfbp)-2-oligodeoxynucleotides for prostate tumor therapy |
| CA2429814C (en) | 2000-12-01 | 2014-02-18 | Thomas Tuschl | Rna interference mediating small rna molecules |
| CA2433680A1 (en) * | 2000-12-28 | 2002-08-01 | Gregory M Arndt | Double-stranded rna-mediated gene suppression |
| EP1386004A4 (en) * | 2001-04-05 | 2005-02-16 | Ribozyme Pharm Inc | MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID |
| WO2003062421A1 (en) | 2002-01-17 | 2003-07-31 | The University Of British Columbia | Bispecific antisense olignucleotides that inhibit igfbp-2 and igfbp-5 and methods of using same |
| KR101238701B1 (ko) * | 2002-08-21 | 2013-03-05 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 암-관련 단백질을 표적으로 하는 알엔에이아이 프로브 |
| SI1530636T1 (sl) * | 2002-08-21 | 2010-12-31 | Stry Liaison Ofiice The University Of British Columbia Umiversity Indu | Zdravljenje melanoma z zniĹľanjem nivojev klusterina |
| AU2003295600A1 (en) * | 2002-11-14 | 2004-06-15 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| US7250496B2 (en) * | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
-
2003
- 2003-08-21 KR KR1020117025408A patent/KR101238701B1/ko not_active Expired - Fee Related
- 2003-08-21 EP EP10010458.7A patent/EP2263679B1/en not_active Expired - Lifetime
- 2003-08-21 AU AU2003258426A patent/AU2003258426B2/en not_active Ceased
- 2003-08-21 KR KR1020107028249A patent/KR101117673B1/ko not_active Expired - Fee Related
- 2003-08-21 EP EP03792075A patent/EP1532249A2/en not_active Ceased
- 2003-08-21 JP JP2005501198A patent/JP4717633B2/ja not_active Expired - Fee Related
- 2003-08-21 WO PCT/CA2003/001277 patent/WO2004018676A2/en not_active Ceased
- 2003-08-21 KR KR1020057002963A patent/KR101212512B1/ko not_active Expired - Fee Related
- 2003-08-21 NZ NZ552872A patent/NZ552872A/en not_active IP Right Cessation
- 2003-08-21 CA CA2494766A patent/CA2494766C/en not_active Expired - Fee Related
- 2003-08-21 US US10/646,436 patent/US8252918B2/en not_active Expired - Fee Related
- 2003-08-21 CA CA2882443A patent/CA2882443C/en not_active Expired - Fee Related
-
2005
- 2005-02-02 IL IL166658A patent/IL166658A/en not_active IP Right Cessation
- 2005-03-17 NO NO20051423A patent/NO334573B1/no not_active IP Right Cessation
-
2006
- 2006-02-23 US US11/276,300 patent/US7964717B2/en not_active Expired - Fee Related
-
2008
- 2008-05-06 US US12/116,083 patent/US7820635B2/en not_active Expired - Fee Related
-
2009
- 2009-02-22 IL IL197159A patent/IL197159A/en not_active IP Right Cessation
-
2010
- 2010-06-04 JP JP2010128382A patent/JP5171887B2/ja not_active Expired - Fee Related
- 2010-07-28 US US12/845,521 patent/US8759308B2/en not_active Expired - Fee Related
- 2010-11-09 JP JP2010250838A patent/JP5662766B2/ja not_active Expired - Fee Related
-
2012
- 2012-02-24 US US13/404,741 patent/US9487777B2/en not_active Expired - Fee Related
- 2012-09-14 NO NO20121038A patent/NO337130B1/no not_active IP Right Cessation
-
2013
- 2013-03-28 JP JP2013067754A patent/JP2013150624A/ja active Pending
-
2014
- 2014-06-24 IL IL233352A patent/IL233352A0/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO20121038L (no) | RNAi-prober som malsoker cancer-relaterte proteiner | |
| Weber et al. | Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference | |
| NO338310B1 (no) | Sammensetninger og anvendelser av disse for behandling av prostata- og andre cancere | |
| US20100055783A1 (en) | Nucleic acid compounds for inhibiting ras gene expression and uses thereof | |
| Liu et al. | Survivin knockdown combined with apoptin overexpression inhibits cell growth significantly | |
| AU2007216630B2 (en) | RNAi probes targeting cancer-related proteins | |
| NZ538287A (en) | RNAi probes targeting cancer-related proteins | |
| CA2680058C (en) | Induction of apoptosis and inhibition of cell proliferation through modulation of carnitine palmitoyltransferase 1c activity | |
| WO2012161539A2 (ko) | ＢＨＲＦ１ 발현 억제를 위한 ｓｉＲＮＡ 및 이를 포함하는 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |