Trial for the novel therapy of chronic hepatitis C by using platform of the RNAi machinery

• Project/Area Number: 19590760
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: MURAKAMI Yoshiki Kyoto University, 医学研究科, 産学官連携准教授 (00397556)
• Co-Investigator(Renkei-kenkyūsha): SHIMOTOHNO Kunitada 慶応義塾大学, 医学部, 教授 (10000259) ; TAJIMA Atsushi 東海大学, 医学部, 講師 (10396864)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: マイクロRNA / C型肝炎ウイルス / 慢性C型肝炎 / HCV / 感染 / マイクロアレイ

Research Abstract

C型肝炎ウイルス(HCV)感染は高率に慢性化し、肝硬変をへて肝細胞癌に発育する。日本人に多い遺伝子型1b感染で高ウイルス量による慢性C型肝炎はインターフェロン治療効果が低い。
(1) HCVゲノム複製を抑制するマイクロRNAを利用して、慢性C型肝炎の制御、(2) ペグインターフェロン+リバビリン併用療法の治療効果別と肝線維化の程度別のマイクロRNA発現プロファイルを作成し、患者個人の遺伝子情報に応じたテーラーメード治療の確立、を目指し体系的な慢性肝炎新規治療への基盤を構築する。

Research Products

• [Journal Article] 3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV (2009)
  • Author(s): Aly HH, Shimotohno K, Hijikata M
  • Journal Title: Biochem Biophys Res Commun 379(2) Pages: 330-334
• [Journal Article] Novel approach for HCV regulation by miR-199a (2009)
  • Author(s): Murakami Y, Ali HH, Tajima A, Inoue I, and Shimotohno K
  • Journal Title: Journal of Hepatology 50 Pages: 453-460
• [Journal Article] Regulation of the hepatitis C virus genome replication by miR-199a* (2009)
  • Author(s): Murakami Y, et al.
  • Journal Title: Journal of Hepatology 50 Pages: 453-460
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia Virus type 1 HBZ protein bypasses the targeting function of ubiquitination (2008)
  • Author(s): Isono O, Ohshima T, Saeki Y, Matsumoto J, Hijikata M, Tanaka K, Shimotohno K
  • Journal Title: J Biol Chem 283(49) Pages: 34273-34282
• [Journal Article] Human T-cell leukemia virus type 1 Tax modulates interferon-alpha signal transduction through competitive usage of the coactivator CBP/p300 (2008)
  • Author(s): Zhang J, Yamada O, Kawagishi K, Araki H, Yamaoka S, Hattori T, Shimotohno K
  • Journal Title: Virology 379(2) Pages: 306-313
• [Journal Article] Synthesis and evaluation of 5'-modified 2'-deoxyadenosine analogues as anti-hepatitis C virus agents (2008)
  • Author(s): Ikejiri M, Ohshima T, Fukushima A, Shimotohno K, Maruyama T
  • Journal Title: Bioorg Med Chem Lett 18(16) Pages: 4638-4641
• [Journal Article] Impact of hepatitis B Virus (HBV) X Gene Integration in Liver Tissue on Hepatocellular Carcinoma Development in Serologically HBV-Negative Chronic Hepatitis C Patients (2008)
  • Author(s): Toyoda H, kumada T, kaneoka Y, and murakami Y
  • Journal Title: Journal of Hepatology 48 Pages: 43-50
• [Journal Article] Integration of Hepatitis B Virus DNA into the Myeloid/Lymphoid or Mixed-Lineage leukemia (MLL4) Gene and Rearrangements of MLL4 in Human Hepatocellular Carcinoma (2008)
  • Author(s): Saigo K, Yoshida K, Ikeda R, Sakamoto Y, Murakami Y, Urashima T, Asano T, kenmochi T, and Inoue I
  • Journal Title: Hum Mutat 29 Pages: 703-8
• [Journal Article] Integration of Hepatitis B Virus DNA into the Myeloid/Lymphoid or Mixed-Lineage Leukemia (MLL4) gene and rearrangements of MLL4 in Human Hepatocellular Carcinoma (2008)
  • Author(s): Saigo K, Yoshida K, Ikeda R, Sakamoto Y, Murakami Y, et al.
  • Journal Title: Human Mutation 29 Pages: 703-708
  • Peer Reviewed
• [Journal Article] Impact of Hepatitis B Virus (HBV) X Gene Integration in Liver Tissue on Hepatocellular Cafcinoma Development in Serologically HBV-Negative Chronic Hepatitis C Patients. (2008)
  • Author(s): Toyoda H, Kumada T, Kaneoka Y, and Murakami Y
  • Journal Title: Journal of Hepatology. 48 Pages: 43-50
  • Peer Reviewed
• [Journal Article] Integration of Hepatitis B Virus DNA into the Myeloid/Lymphoid or Mixed-Lineage Leukemia (MLL4) Gene and Rearrang ements of MLL4 in Human Hepatocellular Carcinoma. (2008)
  • Author(s): Saigo K, Yoshida K, Ikeda R, Sakamoto Y, Murakami Y, Urashima T, Asano T, Kenmochi T, and Inoue I.
  • Journal Title: Human mutation (in press)
  • Peer Reviewed
• [Journal Article] The lipid droplet is an important organelle for hapatitis C virus production (2007)
  • Author(s): Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K.
  • Journal Title: Nat Cell Biol 9(9) Pages: 1089-9710
• [Journal Article] Anti-hepatitis C virus activity of tamoxifen reveals the functional association of estrogen receptor with viral RNA polymerase NS5B (2007)
  • Author(s): Watashi K, Inoue D, Hijikata M, Goto K, Aly HH, Shimotohno K
  • Journal Title: J Biol Chem 282(45) Pages: 32765-32772
• [Journal Article] Chemical genetics approach to hepatitis C virus replication : cyclophilin as a target for anti-hepatitis C virus strategy (2007)
  • Author(s): Watashi K, Shimotohno K
  • Journal Title: Rev Med Virol 17 Pages: 245-252
• [Journal Article] In vitro infection of immortalized primary hepatocytes by HCV genotype 4a and inhibition of virus replication by cyclosporin (2007)
  • Author(s): El-Farrash MA, aly HH, Watashi K, Hijikata M, Egawa H, Shimotohno K
  • Journal Title: Microbiol Immunol 51(1) Pages: 127-133
• [Journal Article] Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes (2007)
  • Author(s): Aly HH, Watashi K, Hijikata M, Kaneko H, Takada Y, Egawa H, uemoto S, Shimotohno K
  • Journal Title: J Hepatol 46(1) Pages: 26-36
• [Journal Article] Helper virus-independent trans-replication of hepatitis C virus-derived minigenome (2007)
  • Author(s): Zhang J, Yamada O, Yoshida H, Sakamoto T, Araki H, Shimotohno K
  • Journal Title: Biochem Biophys Res Commun 352(1) Pages: 170-176
• [Presentation] A novel approach to identify cancer related gene in hepatocellular carcinoma (2008)
  • Author(s): 村上善基, その, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-28
• [Presentation] Aberrant expression of miR-224 has a potential for hepatocarcinogenesis (2008)
  • Author(s): Murakami Y, Okanoue T and Shimotohno K
  • Organizer: JCA 67^<th> Annual meeting
  • Place of Presentation: Nagoya
• [Presentation] Novel approach for HCV regulation by mi RNA (2007)
  • Author(s): 村上善基、その他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2007-10-04
• [Presentation] Novel approach for HCV regulation by using miRNA (2007)
  • Author(s): Murakami Y, Ali HH, Hijikata M, and Shimotohno K
  • Organizer: JCA 66^<th> Annual meeting
  • Place of Presentation: Yokohama
• [Book] マイクロアレイを用いたmiRNAの大規模発現解析RNA実験ノート (2008)
  • Author(s): 村上善基、安田剛
  • Publisher: 羊土社
• [Book] RNA実験ノート (2008)
  • Author(s): 村上善基、安田剛
  • Total Pages: 134
  • Publisher: 羊土社
• [Patent(Industrial Property Rights)] C型肝炎ウイルスの複製を制御するマイクロRNA (2007)
  • Industrial Property Number: 2007-091723
  • Filing Date: 2007-03-30