2004 Fiscal Year Final Research Report Summary
Therapeutic application of RNA interference to suppress hepatitis C virus replication
| Project/Area Number |
15590629
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SAKAMOTO Naoya Tokyo Medical and Dental Univ., Dept.of Gastroenteorology and Hepatology, Instructor, 医学部・附属病院, 助手 (10334418)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Mamoru Tokyo Medical and Dental Univ., Dept.of Gastroenteorology and Hepatology, Professor, 大学院・医歯学総合研究科, 教授 (10175127)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hepatitis Ci virus / HCV replicon system / RNA interference / small interfering RNA / adenovirus vector / molecular targeted drug / antiviral therapy / gene therapy |
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| Research Abstract |
Small interfering RNAs (siRNAs) efficiently inhibit gene expression by RNA interference. Here, we report efficient inhibition, by both synthetic and vector-derived siRNAs, of hepatitis C virus (HCV) replication, as well as viral protein synthesis, using an HCV replicon system. The siRNAs were designed to target the 5' -untranslated region (5' -UTR) of the HCV genome, which has an internal ribosomal entry site for translation of the entire viral polyprotein. Moreover, 5' -UTR is the most conserved throughout the genome, making it an ideal target for siRNA. Importantly, we have identified a very effective site within 5' -UTRR, where ^〜80% suppression of HCV replication was achieved with concentrations of siRNA as low as 2.5 nM. Furthermore, DNA-based vectors expressing siRNA against HCV also were effective, which might allow efficient gene delivery of RNAi into hepatocytes in vivo using virus vectors. Taken together, our results support the feasibility of utilizing siRNA-based gene therapy to inhibit HCV replication, which may prove valuable in the therapy of hepatitis C.
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Research Products
(13 results)
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[Journal Article] Down-regulation of p27Kip1 promotes cell proliferation of rat neonatal cardiomyocytes induced by nuclear expression of cyclin D1 and CDK4 : Evidence for impaired Skp2-dependent degradation of, p27 in terminal differentiation.2004
Author(s)
Tamamori-Adachi M, Hayashida K, Nobori K, Omizu C, Yamada K, Sakamoto N, Kamura T, Fukuda K, Ogawa S, Nakayama KI, Kitajima S
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Journal Title
J Biol Chem 279
Pages: 50429-50436
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of hepatitis C virus replication by interferon regulatory factor-1.2004
Author(s)
Kanazawa N, Kurosaki M, Sakamoto N, Enomoto N, Itsui Y, Yamashiro T, Tanabe Y, Maekawa S, Nakagawa M, Chen CH, Oshima S, Nakamura T, Kato T, Wakita T, Watanabe M.
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Journal Title
J Virol 78(18)
Pages: 9713-9720
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Introduction of NS5A Mutations Enables Subgenomic HCV-Replicon Derived from Chimpanzee-Infectious HC-J4 Isolate to Replicate Efficiently in Huh-7 Cells.2004
Author(s)
Maekawa S, Enomoto N, Sakamoto N, Kurosaki M, Ueda E, Kohashi T, Watanabe H, Chen CH, Yamashiro T, Tanabe Y, Kanazawa N, Nakagawa M, Sato C, Watanabe M.
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Journal Title
J Viral Hepatitis 11
Pages: 394-403
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Synergistic inhibition of intracellular hepatitis C virus replication by combination of ribavirin and interferon-alpha.2004
Author(s)
Tanabe Y, Sakamoto N, Enomoto N, Kurosaki M, Ueada E, Maekawa S, Yamashiro T, Nakagawa M, Chen CH, Kanazawa N, Watanabe M.
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Journal Title
J Infect Dis 189
Pages: 1129-1139
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived siRNAs.2003
Author(s)
Yokota T, Sakamoto N, Enomoto N, Tanabe Y, Miyagishi M, Maekawa S, Ye L, Kurosaki M, Taira K, Watanabe M, Mizusawa H.
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Journal Title
EMBO Reports. 4
Pages: 1-7
Description
「研究成果報告書概要(欧文)」より
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