JP6333739B2 - 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 - Google Patents
遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 Download PDFInfo
- Publication number
- JP6333739B2 JP6333739B2 JP2014558247A JP2014558247A JP6333739B2 JP 6333739 B2 JP6333739 B2 JP 6333739B2 JP 2014558247 A JP2014558247 A JP 2014558247A JP 2014558247 A JP2014558247 A JP 2014558247A JP 6333739 B2 JP6333739 B2 JP 6333739B2
- Authority
- JP
- Japan
- Prior art keywords
- oligonucleotide
- seq
- oligonucleotides
- gene
- nos
- 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
- 108091034117 Oligonucleotide Proteins 0.000 title claims description 257
- 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 title description 99
- 230000014509 gene expression Effects 0.000 title description 41
- 230000001105 regulatory effect Effects 0.000 title description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 58
- 101150022024 MYCN gene Proteins 0.000 claims description 53
- 210000004027 cell Anatomy 0.000 claims description 42
- 102000039446 nucleic acids Human genes 0.000 claims description 39
- 108020004707 nucleic acids Proteins 0.000 claims description 39
- 230000000295 complement effect Effects 0.000 claims description 34
- 150000007523 nucleic acids Chemical class 0.000 claims description 31
- 206010028980 Neoplasm Diseases 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 19
- 125000003729 nucleotide group Chemical group 0.000 claims description 16
- 239000002773 nucleotide Substances 0.000 claims description 15
- -1 proclitaxel Chemical compound 0.000 claims description 11
- 229960004562 carboplatin Drugs 0.000 claims description 10
- 190000008236 carboplatin Chemical compound 0.000 claims description 10
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 10
- 229960004316 cisplatin Drugs 0.000 claims description 10
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
- 229960004528 vincristine Drugs 0.000 claims description 9
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 9
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 9
- 229960005420 etoposide Drugs 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 206010029260 Neuroblastoma Diseases 0.000 claims description 7
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims description 7
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 6
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 5
- 208000000172 Medulloblastoma Diseases 0.000 claims description 5
- 201000000582 Retinoblastoma Diseases 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
- 102000053602 DNA Human genes 0.000 claims description 4
- 108020004414 DNA Proteins 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 208000008383 Wilms tumor Diseases 0.000 claims description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 229960004397 cyclophosphamide Drugs 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 201000008026 nephroblastoma Diseases 0.000 claims description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000000144 pharmacologic effect Effects 0.000 claims description 3
- MWWSFMDVAYGXBV-FGBSZODSSA-N (7s,9s)-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-FGBSZODSSA-N 0.000 claims description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 2
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
- 108010024976 Asparaginase Proteins 0.000 claims description 2
- 102000015790 Asparaginase Human genes 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 2
- 206010009253 Clear cell sarcoma of the kidney Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 2
- 108010036949 Cyclosporine Proteins 0.000 claims description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
- 108010092160 Dactinomycin Proteins 0.000 claims description 2
- 206010014967 Ependymoma Diseases 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 208000021309 Germ cell tumor Diseases 0.000 claims description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- 206010023774 Large cell lung cancer Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 claims description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 229930012538 Paclitaxel Natural products 0.000 claims description 2
- 102000005157 Somatostatin Human genes 0.000 claims description 2
- 108010056088 Somatostatin Proteins 0.000 claims description 2
- 208000000389 T-cell leukemia Diseases 0.000 claims description 2
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims description 2
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 claims description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 2
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 claims description 2
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 claims description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 2
- 229960003272 asparaginase Drugs 0.000 claims description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 claims description 2
- 229960001561 bleomycin Drugs 0.000 claims description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
- 229960002092 busulfan Drugs 0.000 claims description 2
- 229960004117 capecitabine Drugs 0.000 claims description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
- 229960004630 chlorambucil Drugs 0.000 claims description 2
- 229960001265 ciclosporin Drugs 0.000 claims description 2
- 208000030748 clear cell sarcoma of kidney Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 229930182912 cyclosporin Natural products 0.000 claims description 2
- 229960000684 cytarabine Drugs 0.000 claims description 2
- 229960003901 dacarbazine Drugs 0.000 claims description 2
- 229960000640 dactinomycin Drugs 0.000 claims description 2
- 229960000975 daunorubicin Drugs 0.000 claims description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 2
- 229960003668 docetaxel Drugs 0.000 claims description 2
- 229960003265 epirubicin hydrochloride Drugs 0.000 claims description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 2
- 229960005304 fludarabine phosphate Drugs 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
- 208000006359 hepatoblastoma Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 229960001176 idarubicin hydrochloride Drugs 0.000 claims description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 2
- 229960001101 ifosfamide Drugs 0.000 claims description 2
- 229960000779 irinotecan hydrochloride Drugs 0.000 claims description 2
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 claims description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 claims description 2
- 201000009546 lung large cell carcinoma Diseases 0.000 claims description 2
- 201000005243 lung squamous cell carcinoma Diseases 0.000 claims description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 2
- 229960001924 melphalan Drugs 0.000 claims description 2
- 229960001156 mitoxantrone Drugs 0.000 claims description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 2
- 230000000955 neuroendocrine Effects 0.000 claims description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 2
- 229960001756 oxaliplatin Drugs 0.000 claims description 2
- 229960001592 paclitaxel Drugs 0.000 claims description 2
- 208000028591 pheochromocytoma Diseases 0.000 claims description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 2
- 229960000624 procarbazine Drugs 0.000 claims description 2
- 229930002330 retinoic acid Natural products 0.000 claims description 2
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 2
- 229960000553 somatostatin Drugs 0.000 claims description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims description 2
- 229960001052 streptozocin Drugs 0.000 claims description 2
- 206010042863 synovial sarcoma Diseases 0.000 claims description 2
- 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 claims description 2
- 229960003087 tioguanine Drugs 0.000 claims description 2
- 229960000303 topotecan Drugs 0.000 claims description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 2
- 229960001727 tretinoin Drugs 0.000 claims description 2
- 229960003048 vinblastine Drugs 0.000 claims description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- 229960004355 vindesine Drugs 0.000 claims description 2
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 claims description 2
- 229960002066 vinorelbine Drugs 0.000 claims description 2
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 2
- SUHQNCLNRUAGOO-KQCZLNONSA-N (4s,5r,6r,7s,8r)-4,6,7,8,9-pentahydroxy-5-[(2-hydroxyacetyl)amino]-2-oxononanoic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](NC(=O)CO)[C@@H](O)CC(=O)C(O)=O SUHQNCLNRUAGOO-KQCZLNONSA-N 0.000 claims 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims 1
- 101150023956 ALK gene Proteins 0.000 claims 1
- 108020004491 Antisense DNA Proteins 0.000 claims 1
- 101150115284 BIRC5 gene Proteins 0.000 claims 1
- 101150017888 Bcl2 gene Proteins 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
- 101150039798 MYC gene Proteins 0.000 claims 1
- 229930192392 Mitomycin Natural products 0.000 claims 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims 1
- 101150005816 PLK4 gene Proteins 0.000 claims 1
- 239000003816 antisense DNA Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims 1
- 229960001428 mercaptopurine Drugs 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 229960004857 mitomycin Drugs 0.000 claims 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims 1
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 claims 1
- 229960002110 vincristine sulfate Drugs 0.000 claims 1
- 239000000178 monomer Substances 0.000 description 92
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 63
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 58
- 108091093037 Peptide nucleic acid Proteins 0.000 description 49
- 108700012912 MYCN Proteins 0.000 description 34
- 108700026495 N-Myc Proto-Oncogene Proteins 0.000 description 34
- 102100030124 N-myc proto-oncogene protein Human genes 0.000 description 33
- 125000002652 ribonucleotide group Chemical group 0.000 description 17
- 108091028664 Ribonucleotide Proteins 0.000 description 16
- 239000002336 ribonucleotide Substances 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- 230000000692 anti-sense effect Effects 0.000 description 15
- 108020004999 messenger RNA Proteins 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 108020004459 Small interfering RNA Proteins 0.000 description 14
- 239000002246 antineoplastic agent Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000004055 small Interfering RNA Substances 0.000 description 13
- 230000014616 translation Effects 0.000 description 13
- 238000013518 transcription Methods 0.000 description 12
- 230000035897 transcription Effects 0.000 description 12
- 238000013519 translation Methods 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 108010002687 Survivin Proteins 0.000 description 10
- 239000000074 antisense oligonucleotide Substances 0.000 description 10
- 238000012230 antisense oligonucleotides Methods 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 10
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 9
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 8
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 8
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 8
- 108091012583 BCL2 Proteins 0.000 description 8
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 229940127089 cytotoxic agent Drugs 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 7
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 7
- 101000582914 Homo sapiens Serine/threonine-protein kinase PLK4 Proteins 0.000 description 7
- 102100030267 Serine/threonine-protein kinase PLK4 Human genes 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 108010025020 Nerve Growth Factor Proteins 0.000 description 6
- 102000015336 Nerve Growth Factor Human genes 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 229940053128 nerve growth factor Drugs 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 230000004913 activation Effects 0.000 description 5
- 229940044683 chemotherapy drug Drugs 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000005547 deoxyribonucleotide Substances 0.000 description 5
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 5
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 5
- 230000002452 interceptive effect Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 230000007170 pathology Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 101100468589 Arabidopsis thaliana RH30 gene Proteins 0.000 description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 108091093094 Glycol nucleic acid Proteins 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 150000008209 arabinosides Chemical class 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000004091 Caspase-8 Human genes 0.000 description 3
- 108090000538 Caspase-8 Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 101000585703 Homo sapiens Protein L-Myc Proteins 0.000 description 3
- 101001091538 Homo sapiens Pyruvate kinase PKM Proteins 0.000 description 3
- 101000712958 Homo sapiens Ras association domain-containing protein 1 Proteins 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 108700011259 MicroRNAs Proteins 0.000 description 3
- 108091057508 Myc family Proteins 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 102100030128 Protein L-Myc Human genes 0.000 description 3
- 102100034911 Pyruvate kinase PKM Human genes 0.000 description 3
- 102100033243 Ras association domain-containing protein 1 Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000001613 neoplastic effect Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 150000004713 phosphodiesters Chemical class 0.000 description 3
- 239000004626 polylactic acid Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 150000008574 D-amino acids Chemical class 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 241000233805 Phoenix Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 206010065867 alveolar rhabdomyosarcoma Diseases 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 150000008300 phosphoramidites Chemical class 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 208000037826 rabdomyosarcoma Diseases 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000014493 regulation of gene expression Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- REUYSHQBEXUIRY-UHFFFAOYSA-N 2-[2-(9h-fluoren-9-ylmethoxycarbonylamino)ethyl-[2-(5-methyl-2,4-dioxopyrimidin-1-yl)acetyl]amino]acetic acid Chemical compound O=C1NC(=O)C(C)=CN1CC(=O)N(CC(O)=O)CCNC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 REUYSHQBEXUIRY-UHFFFAOYSA-N 0.000 description 1
- YPTOIRLDQISSCH-UHFFFAOYSA-N 2-[[2-[4-(benzhydryloxycarbonylamino)-2-oxopyrimidin-1-yl]acetyl]-[2-(9h-fluoren-9-ylmethoxycarbonylamino)ethyl]amino]acetic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NCCN(CC(=O)O)C(=O)CN(C(N=1)=O)C=CC=1NC(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 YPTOIRLDQISSCH-UHFFFAOYSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#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
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- GXGKKIPUFAHZIZ-UHFFFAOYSA-N 5-benzylsulfanyl-2h-tetrazole Chemical compound C=1C=CC=CC=1CSC=1N=NNN=1 GXGKKIPUFAHZIZ-UHFFFAOYSA-N 0.000 description 1
- GONFBOIJNUKKST-UHFFFAOYSA-N 5-ethylsulfanyl-2h-tetrazole Chemical compound CCSC=1N=NNN=1 GONFBOIJNUKKST-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 206010010539 Congenital megacolon Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 208000004592 Hirschsprung disease Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- CXQCLLQQYTUUKJ-ALWAHNIESA-N beta-D-GalpNAc-(1->4)-[alpha-Neup5Ac-(2->8)-alpha-Neup5Ac-(2->3)]-beta-D-Galp-(1->4)-beta-D-Glcp-(1<->1')-Cer(d18:1/18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@@H](CO)O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 CXQCLLQQYTUUKJ-ALWAHNIESA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000007068 beta-elimination reaction Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid 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
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 238000002653 magnetic therapy Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 208000022499 mismatch repair cancer syndrome Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 108700024542 myc Genes Proteins 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000002640 oxygen therapy Methods 0.000 description 1
- 108700025694 p53 Genes Proteins 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical group [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920003217 poly(methylsilsesquioxane) Polymers 0.000 description 1
- 229920005597 polymer membrane Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/1135—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 against oncogenes or tumor suppressor genes
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C12N2310/11—Antisense
-
- 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
- C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
- C12N2310/3181—Peptide nucleic acid, PNA
-
- 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
- C12N2310/322—2'-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
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
-
- 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
- C12N2310/3233—Morpholino-type ring
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/31—Combination therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Neurology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Virology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
Description
・任意で、好ましくは3’末端及び/又は5’末端において、担体(一般的に1〜30残基からなる)と結合したPNA型オリゴヌクレオチド;又は
・PNA型オリゴヌクレオチドであって、前記PNAは標準的なグリシンのH原子以外の置換基を有する少なくとも1つのα炭素(C−α)の主鎖を含む、PNA型オリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び任意で少なくとも1つの修飾されたヌクレオチド(モノマー)(例えば2’−0−メチルRNAモノマー、2’−フルオロRNAモノマー)、又はLNA、メチルホスホネートLNA、BNA、UNA、GNA、ANA、FANA、ENA、DNG及びRNGの中から選択される核酸の少なくとも1つのモノマー、又はホスホジエステル結合のレベルにおいて修飾されたリボヌクレオチドを含む一本鎖オリゴヌクレオチド;又は
・相互に相補的な二本鎖RNA型オリゴヌクレオチド(siRNA);又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つのLNAモノマーを含む部分的に相補的な二本鎖キメラオリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つの2’−0−(2−メトキシエチル)RNAモノマーを含む二本鎖キメラオリゴヌクレオチド;又は
・DNAモノマー(典型的なデオキシリボヌクレオチド)及び少なくとも1つのLNAモノマーを含む一本鎖キメラオリゴヌクレオチド;又は
・DNAモノマー(典型的なデオキシリボヌクレオチド)並びに少なくとも1つの2’−フルオロRNAモノマー、又はLNA、メチルホスホネートLNA、BNA、UNA、GNA、ENA、ANA、FANA、DNG及びRNGの中から選択される核酸の少なくとも1つのモノマーを含むオリゴヌクレオチド;
を用いることができる。
・RNAモノマー(典型的なリボヌクレオチド)を含む相互に相補的な二本鎖オリゴヌクレオチド(siRNA);又は
・RNAモノマー(典型的なリボヌクレオチド)並びにリボースレベル及び/又はホスホジエステル結合のレベルにおいて修飾される少なくとも1つのRNAモノマーを含む一本鎖オリゴヌクレオチド;又は
・DNAモノマー(典型的なデオキシヌクレオチド)及び少なくとも1つのホスホロチオエートDNAモノマーを含む一本鎖キメラオリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つの2’−0−(2−メトキシエチル)RNAモノマーを含む二本鎖キメラオリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つの2’0−メチル化RNAモノマーを含む二本鎖キメラオリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つの2’−フルオロRNAモノマーを含む二本鎖キメラオリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つのLNAモノマーを含む二本鎖キメラオリゴヌクレオチド;又は
・RNAモノマー(典型的なリボヌクレオチド)及び少なくとも1つのアラビノシドRNAモノマーを含む二本鎖キメラオリゴヌクレオチド;又は
・DNAモノマー(典型的なデオキシヌクレオチド)及び少なくとも1つのLNAモノマーを含む一本鎖キメラオリゴヌクレオチド;又は
・モルホリノモノマを含む一本鎖オリゴヌクレオチド;又は
・PNA型オリゴヌクレオチドであって、前記PNAは標準的なグリシンのH原子以外の置換基を有する、少なくとも1つのα炭素(C−α)の主鎖を含み、好ましくは該置換基はアルギニン又はリジンの側鎖である、PNA型オリゴヌクレオチド;又は
・DNAモノマー(典型的なデオキシヌクレオチド)並びにPNA、LNA、LNAメチルホスホネート、BNA、UNA、GNA、ENA、DNG及びRNGの中から選択される核酸の少なくとも1つのモノマーを含むオリゴヌクレオチド;
を用いることができる。
オリゴヌクレオチドの化学合成
オリゴヌクレオチドの化学合成は、保護基である5’−OH上の4’−ジメトキシトリチル(DMTr)、及び3’−リン酸基上のβ−シアノエチルで修飾されたDNAヌクレオシドホスホロアミダイトの使用に基づき;保護基はまた、さもなければ反応性が高すぎる第一級アミン(核塩基複素環)のために用いられる。
本発明に記載されるパラメータに従って選択及び設計された本発明のオリゴヌクレオチドが、遺伝子の転写を選択的に妨害するために機能することを実証するために、MYCN遺伝子に対するPNA型オリゴヌクレオチドを設計及び合成した;これらを表1に示す。
本発明に記載されるパラメータに従って選択及び設計された本発明のオリゴヌクレオチドが、標的遺伝子の翻訳を選択的に妨害するために機能することを実証するために、MYCN遺伝子に対する配列番号26〜36を有するアンチセンスオリゴヌクレオチドを設計し、合成し、そして実験的にインビトロで分析した。これらを表3に示す。
本発明のオリゴヌクレオチドの標的遺伝子の発現を調節する能力を評価するために、メッセンジャーRNAの量を減少させるこれらの能力を、リアルタイムPCR技術を用いて分析した。
・アンチセンスオリゴヌクレオチドsiRNA及びsiRNAギャップマー(即ち、3’又は5’末端において化学的に修飾された核酸の1又は複数のモノマーを含むオリゴヌクレオチドである一方で、中央の部分において、これらが、修飾されていない、又はホスホロチオエート結合としてホスホジエステル結合のレベルにおいて修飾される核酸のモノマーを有する)を200nMにおいて用い;
・ホスホロチオエートDNAモノマー、RNAアンチジーンオリゴヌクレオチド(agRNA)を含むアンチセンスオリゴヌクレオチド、並びにDNAモノマー及びLNAモノマーを含むオリゴヌクレオチドを10μΜにおいて用い;
・モルホリノオリゴヌクレオチドを1μΜの濃度において投与し;そして
・PNAオリゴヌクレオチドを1μΜの濃度において投与した。
・神経芽細胞モデルとして、細胞株Kelly、IMR−32(MYCN遺伝子を増幅及び過剰発現する)並びにSKNBE2c及びLANl(MYCN遺伝子を増幅及び過剰発現し、そしてp53遺伝子は突然変異誘導される)を使用し;
・横紋筋肉腫(rabdomiosarcoma)モデルとして、MYCN遺伝子を増幅及び過剰発現する細胞株RH30を使用し;
・ウィルムス腫瘍(rabdomiosarcoma)モデルとして、MYCN遺伝子を増幅及び過剰発現する細胞株WiT49を使用し;
・網膜芽細胞腫(rabdomiosarcoma)モデルとして、MYCN遺伝子を増幅及び過剰発現する細胞株Y79を使用し;
・小細胞肺癌のモデルとして、MYCN遺伝子を増幅及び過剰発現する細胞株H69を使用した。
本発明のオリゴヌクレオチドの遺伝子調節能力を評価するために、細胞生存率に関するこれらの投与の効果を測定した。
PNAオリゴヌクレオチドに関する限り、MYCN遺伝子の転写を阻害するこれらの能力及びKelly細胞の増殖に関する結果を表1に示す。表6は、分析されるPNAの様々な濃度において増殖するKelly細胞の値(パーセンテージの形態)を示す。
本発明をサポートするために、表10に要約されるオリゴヌクレオチドも合成した。特に、表10は、オリゴヌクレオチド配列、配列番号、(G+C)含量のパーセンテージ値及び遺伝子を示し、合成されたオリゴヌクレオチドに対する。オリゴヌクレオチドの合成は、実施例1のように達成された。
Claims (15)
- 標的遺伝子のアンチセンスDNA鎖に相補的な一本鎖アンチジーンオリゴヌクレオチドであって、6〜30ヌクレオチドを含み、前記オリゴヌクレオチドが、配列番号2、4、5、6、46、68〜84から選択される、オリゴヌクレオチド。
- 前記オリゴヌクレオチドが、12〜24ヌクレオチドを含む、請求項1に記載のオリゴヌクレオチド。
- 請求項1又は2に記載のオリゴヌクレオチドにおいて、
配列番号2、4、5、6、68及び69が、MYCN遺伝子に対するものであり;
配列番号70〜74が、MYC遺伝子に対するものであり;
配列番号75及び76が、BIRC5遺伝子に対するものであり;
配列番号77〜79が、ALK遺伝子に対するものであり;
配列番号80〜82が、BCL2遺伝子に対するものであり;及び、
配列番号83及び84が、PLK4遺伝子に対するものである、
前記オリゴヌクレオチド。 - 前記オリゴヌクレオチドが、前記オリゴヌクレオチドの3’及び/又は5’末端において、担体配列と結合している、請求項1〜3のいずれか一項に記載のオリゴヌクレオチド。
- 前記担体配列が、配列番号47〜56からなる群から選択される、請求項4に記載のオリゴヌクレオチド。
- 前記オリゴヌクレオチドが、天然の核酸、化学的に修飾された天然の核酸、合成核酸、化学的に修飾された合成核酸、又はそれらの組み合わせ、からなる分子である、請求項1〜5のいずれか一項に記載のオリゴヌクレオチド。
- 前記天然の核酸又は化学的に修飾された天然の核酸が、DNA又はRNAから選択され、前記合成核酸又は前記化学的に修飾された合成核酸が、PNA、LNA又はモルホリノから選択される、請求項6に記載のオリゴヌクレオチド。
- 1)前記DNA分子が、少なくとも1つのLNA、メチルホスホネート−LNA、BNA、RNG、DNG、GNA、UNA、ENA、ANA、F−ANA、PNA、G−PNA若しくはモルホリノヌクレオチドを含むか;又は、2’0−メチル、2’0−メトキシエチル若しくは2’−フルオロRNAヌクレオチドを含む;あるいは、
2)前記少なくとも1つのRNA分子が、2’0−エチルヌクレオチド、2’0−メトキシエチルヌクレオチド、2’−フルオロヌクレオチドの中から選択される前記少なくとも1つのRNAヌクレオチド;又は、LNA、メチルホスホネートLNA、BNA、RNG、DNG、GNA、UNA、ENA、ANA、F−ANA、PNA、G−PNA若しくはモルホリノの中から選択される核酸の少なくとも1つのヌクレオチドを含む、
請求項7に記載のオリゴヌクレオチド。 - 前記DNA分子又は前記RNA分子は、そのホスホジエステル結合が、ホスホロチオエート結合として修飾された少なくとも1つのヌクレオチドを含む、請求項7又は8に記載のオリゴヌクレオチド。
- 前記PNAが、修飾された主鎖を有し、α炭素が、置換基としてアルギニン又はリジンの側鎖を有する、請求項7〜9のいずれか一項に記載のオリゴヌクレオチド。
- 請求項1〜10のいずれか一項に記載の少なくとも1つのオリゴヌクレオチド、及び少なくとも1つの医薬的に許容される賦形剤を含む組成物。
- 薬理作用を有する、NGF、ソマトスタチン、レチノイン酸、アクチノマイシンD、アスパラギナーゼ、ブレオマイシン、ブスルファン、カペシタビン、カルボプラチン、シクロホスファミド、シクロスポリン、シスプラチン、シタラビン、クロラムブシル(clorambucil)、ダカルバジン、ダウノルビシン、ドセタキセル、塩酸ドキソルビシン、塩酸エピルビシン、エトポシド、リン酸フルダラビン、フルオロウラシル、ゲムシタビン、塩酸イダルビシン、ヒドロキシ尿素、イソホスファミド(ifophosphamide)、塩酸イリノテカン、メルファラン、メルカプトプリン、メトトレキサート、マイトマイシン、ミトキサントロン、オキサリプラチン、パクリタキセル、プロカルバジン、ラルチトレキセド、ストレプトゾシン、テガフール‐ウラシル、テモゾロミド、チオグアニン、チオテパ(thiotepe)、トポテカン、ビンブラスチン、硫酸ビンクリスチン、ビンデシン及びビノレルビンからなる群から選択された化合物と組み合わせた、請求項1〜10のいずれか一項に記載の少なくとも1つのオリゴヌクレオチドを含む、組成物。
- 配列番号1、及びカルボプラチン又はエトポシド又はシスプラチン又はビンクリスチンとの組み合わせ;あるいは、
配列番号5、及びカルボプラチン又はエトポシド又はシスプラチン又はビンクリスチンとの組み合わせを含む、請求項12に記載の組成物。 - 医薬としての使用のための、請求項11〜13のいずれか一項に記載の組成物。
- 腫瘍の治療に使用するための組成物であって、
前記腫瘍が、成人又は小児の腫瘍であり、ここで前記腫瘍が、神経芽細胞腫、網膜芽細胞腫、髄芽細胞腫、上衣腫、褐色細胞腫、胚性癌、胚細胞腫瘍、肺胞横紋筋肉腫、胚性横紋筋肉腫、ウィルムス腫瘍、腎臓の明細胞肉腫、滑膜肉腫、肝芽細胞腫、急性リンパ性白血病、慢性リンパ性白血病、急性リンパ芽球性白血病、慢性リンパ芽球性白血病、バーキットリンパ腫、急性骨髄性白血病、慢性骨髄性白血病、急性巨核芽球性白血病、B細胞慢性リンパ性白血病、T細胞白血病、リンパ腫、小細胞肺癌(小細胞癌(microcytoma))、肺腺癌、扁平細胞肺癌、定型及び非定型原発性肺癌、大細胞肺癌、大細胞神経内分泌性肺癌、神経膠芽細胞腫、肝細胞癌、基底細胞癌、卵巣腫瘍、乳房腫瘍及び結腸癌からなる群から選択される、
請求項14に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT000275A ITMI20120275A1 (it) | 2012-02-24 | 2012-02-24 | Oligonucleotidi per la modulazione dell'espressione genica e loro usi |
ITMI2012A000275 | 2012-02-24 | ||
PCT/IB2013/051410 WO2013124807A2 (en) | 2012-02-24 | 2013-02-21 | Oligonucleotides for modulating gene expression and uses thereof |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017237889A Division JP2018078893A (ja) | 2012-02-24 | 2017-12-12 | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2015513398A JP2015513398A (ja) | 2015-05-14 |
JP2015513398A5 JP2015513398A5 (ja) | 2016-02-04 |
JP6333739B2 true JP6333739B2 (ja) | 2018-05-30 |
Family
ID=45999941
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014558247A Active JP6333739B2 (ja) | 2012-02-24 | 2013-02-21 | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 |
JP2017237889A Pending JP2018078893A (ja) | 2012-02-24 | 2017-12-12 | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017237889A Pending JP2018078893A (ja) | 2012-02-24 | 2017-12-12 | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 |
Country Status (27)
Country | Link |
---|---|
US (2) | US10023867B2 (ja) |
EP (1) | EP2817407B1 (ja) |
JP (2) | JP6333739B2 (ja) |
KR (1) | KR101992925B1 (ja) |
CN (2) | CN104169421A (ja) |
AR (1) | AR090129A1 (ja) |
AU (2) | AU2013223694B2 (ja) |
BR (1) | BR112014020885B1 (ja) |
CA (1) | CA2864060C (ja) |
CY (1) | CY1120084T1 (ja) |
DK (1) | DK2817407T3 (ja) |
ES (1) | ES2651147T3 (ja) |
HK (1) | HK1201878A1 (ja) |
HU (1) | HUE034846T2 (ja) |
IN (1) | IN2014MN01493A (ja) |
IT (1) | ITMI20120275A1 (ja) |
LT (1) | LT2817407T (ja) |
MA (1) | MA35935B1 (ja) |
NO (1) | NO2817407T3 (ja) |
PL (1) | PL2817407T3 (ja) |
PT (1) | PT2817407T (ja) |
RS (1) | RS56631B1 (ja) |
RU (1) | RU2648140C2 (ja) |
SG (2) | SG11201404852WA (ja) |
SI (1) | SI2817407T1 (ja) |
TN (1) | TN2014000327A1 (ja) |
WO (1) | WO2013124807A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018078893A (ja) * | 2012-02-24 | 2018-05-24 | ビオジェネラ ソチエタ ペル アツィオニ | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013173608A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics, Inc. | Compositions and methods for modulating mecp2 expression |
AU2013262649A1 (en) | 2012-05-16 | 2015-01-22 | Rana Therapeutics, Inc. | Compositions and methods for modulating smn gene family expression |
US10174323B2 (en) | 2012-05-16 | 2019-01-08 | The General Hospital Corporation | Compositions and methods for modulating ATP2A2 expression |
US10837014B2 (en) | 2012-05-16 | 2020-11-17 | Translate Bio Ma, Inc. | Compositions and methods for modulating SMN gene family expression |
US10174315B2 (en) | 2012-05-16 | 2019-01-08 | The General Hospital Corporation | Compositions and methods for modulating hemoglobin gene family expression |
CA2873797A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics Inc. | Compositions and methods for modulating utrn expression |
EP3556402A4 (en) | 2016-12-13 | 2020-08-05 | AM Sciences Inc | PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF HEPATITIS B |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1257665A2 (en) * | 2000-02-14 | 2002-11-20 | Inc. Cytoclonal Pharmaceutics | LIBRARIES OF OPTIMUM SUBSEQUENCE REGIONS OF mRNA AND GENOMIC DNA FOR CONTROL OF GENE EXPRESSION |
CA2447052A1 (en) | 2001-05-17 | 2002-11-21 | Avi Biopharma, Inc. | Combined approach to treatment of cancer using a c-myc antisense oligomer |
EP1448590A4 (en) * | 2002-02-20 | 2004-12-15 | Sirna Therapeutics Inc | INHIBITION INDUCED BY THE INTERFERENCE OF RNA OF THE MYC AND MYB GENES OR OF GENES INTERVENING IN THEIR RESPECTIVE PATHWAYS |
ITMI20030860A1 (it) | 2003-04-29 | 2004-10-30 | Univ Bologna | Metodo per l'inibizione selettiva del gene n-myc |
WO2005045032A2 (en) | 2003-10-20 | 2005-05-19 | Sima Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF EARLY GROWTH RESPONSE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
GB0415263D0 (en) * | 2004-07-07 | 2004-08-11 | Norwegian Radium Hospital Res | Method |
JP2008517627A (ja) * | 2004-10-25 | 2008-05-29 | ノバルティス アクチエンゲゼルシャフト | Torcポリヌクレオチドおよびポリペプチドならびに使用法 |
US7625874B2 (en) * | 2006-04-11 | 2009-12-01 | The Regents Of The University Of California | Compositions and methods for treating diseases associated with T-box and N-Myc |
US20080038783A1 (en) * | 2006-06-29 | 2008-02-14 | Applera Corporation | Compositions and Methods Pertaining to Guanylation of PNA Oligomers |
US20090047295A1 (en) * | 2007-07-12 | 2009-02-19 | Berry David A | Methods and Compositions for Reducing Stemness in Oncogenesis |
WO2010065787A2 (en) * | 2008-12-04 | 2010-06-10 | Curna, Inc. | Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene |
CN102058535B (zh) * | 2010-12-21 | 2013-05-01 | 中国人民解放军总医院 | 叶酸受体靶向的新型脂质体 |
ITMI20120275A1 (it) * | 2012-02-24 | 2013-08-25 | Biogenera Societa A Responsabilita Limitata | Oligonucleotidi per la modulazione dell'espressione genica e loro usi |
-
2012
- 2012-02-24 IT IT000275A patent/ITMI20120275A1/it unknown
-
2013
- 2013-02-21 SG SG11201404852WA patent/SG11201404852WA/en unknown
- 2013-02-21 SG SG10201606946YA patent/SG10201606946YA/en unknown
- 2013-02-21 LT LTEP13716415.8T patent/LT2817407T/lt unknown
- 2013-02-21 CA CA2864060A patent/CA2864060C/en active Active
- 2013-02-21 ES ES13716415.8T patent/ES2651147T3/es active Active
- 2013-02-21 EP EP13716415.8A patent/EP2817407B1/en active Active
- 2013-02-21 HU HUE13716415A patent/HUE034846T2/en unknown
- 2013-02-21 PT PT137164158T patent/PT2817407T/pt unknown
- 2013-02-21 CN CN201380009360.1A patent/CN104169421A/zh active Pending
- 2013-02-21 CN CN202210708144.7A patent/CN115216475A/zh active Pending
- 2013-02-21 DK DK13716415.8T patent/DK2817407T3/en active
- 2013-02-21 KR KR1020147026837A patent/KR101992925B1/ko active IP Right Grant
- 2013-02-21 US US14/379,729 patent/US10023867B2/en active Active
- 2013-02-21 WO PCT/IB2013/051410 patent/WO2013124807A2/en active Application Filing
- 2013-02-21 PL PL13716415T patent/PL2817407T3/pl unknown
- 2013-02-21 AU AU2013223694A patent/AU2013223694B2/en active Active
- 2013-02-21 JP JP2014558247A patent/JP6333739B2/ja active Active
- 2013-02-21 BR BR112014020885-9A patent/BR112014020885B1/pt active IP Right Grant
- 2013-02-21 IN IN1493MUN2014 patent/IN2014MN01493A/en unknown
- 2013-02-21 SI SI201330845T patent/SI2817407T1/en unknown
- 2013-02-21 RU RU2014138198A patent/RU2648140C2/ru active
- 2013-02-21 NO NO13716415A patent/NO2817407T3/no unknown
- 2013-02-21 RS RS20171253A patent/RS56631B1/sr unknown
- 2013-02-22 AR ARP130100546A patent/AR090129A1/es active IP Right Grant
-
2014
- 2014-07-31 TN TNP2014000327A patent/TN2014000327A1/fr unknown
- 2014-09-10 MA MA37342A patent/MA35935B1/fr unknown
-
2015
- 2015-03-10 HK HK15102407.6A patent/HK1201878A1/xx unknown
-
2017
- 2017-12-05 CY CY20171101270T patent/CY1120084T1/el unknown
- 2017-12-12 JP JP2017237889A patent/JP2018078893A/ja active Pending
-
2018
- 2018-06-15 US US16/009,303 patent/US10752900B2/en active Active
- 2018-12-13 AU AU2018278972A patent/AU2018278972A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018078893A (ja) * | 2012-02-24 | 2018-05-24 | ビオジェネラ ソチエタ ペル アツィオニ | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6333739B2 (ja) | 遺伝子発現を調節するためのオリゴヌクレオチド及びこれの使用 | |
Pirollo et al. | Antisense therapeutics: from theory to clinical practice | |
AU2014306416A1 (en) | Compositions and methods for modulating RNA | |
AU2007310982A1 (en) | Nicked or gapped nucleic acid molecules and uses thereof | |
WO2015023941A1 (en) | Oligonucleotides targeting euchromatin regions of genes | |
JP2023518970A (ja) | 安定性の向上を有する修飾オリゴヌクレオチドの合成 | |
TW202006138A (zh) | Fubp1抑制劑用於治療b型肝炎病毒感染之用途 | |
AU2005270917A1 (en) | Gastrin-specific interfering RNA | |
WO2012100172A2 (en) | Methods and compositions for the specific inhibition of hif-1a by double stranded rna | |
CN109477090B (zh) | 微小rna-143衍生物 | |
JP2021505175A (ja) | Fndc3bの発現を調節するためのオリゴヌクレオチド | |
CN114144526B (zh) | Eph2a适配体及其用途 | |
Berk | Alternative scaffolds for systemic delivery of small interfering RNAs | |
US20150167004A1 (en) | Oligonucleotide inhibitors of dna methyltransferases and their use in treating diseases | |
KR20240014533A (ko) | 신규한 유전자 침묵 기술로서의 짧은 듀플렉스 dna 및 이의 용도 | |
CN117858946A (zh) | 作为新型基因沉默技术的非对称短双链体dna及其应用 | |
CN111615558A (zh) | 用于调节erc1表达的寡核苷酸 | |
AU2014200144A1 (en) | Nicked or gapped nucleic acid molecules and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151208 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151208 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160920 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161128 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170321 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170912 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171212 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180327 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180425 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6333739 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |