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DEVELOPMENT OF THERAPY FOR HEPATITIS C USING PROTEIN TRANSDUCTION METHOD

Research Project

Project/Area Number 12557052
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

KOIKE Kazuhiko  TOKYO UNIV., DPT OF MEDICINE, ASSOCIATE PROFESSOR, 医学部・附属病院, 助教授 (80240703)

Co-Investigator(Kenkyū-buntansha) FUJIE Hajime  TOKYO UNIV., DPT OF MEDICINE, ASSISTANT PROF., 医学部・附属病院, 助手
SHINTANI Yoshizumi  TOKYO UNIV., DPT OF MEDICINE, ASSISTANT PROF., 医学部・附属病院, 助手
MORIYA Kyoji  TOKYO UNIV., DPT OF MEDICINE, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (00272550)
ISHOBASHI Kotaro  DAIICHI PHARMACEUTICALS, PRINCIPAL RESEARCHER, 試験研究センター, 主任研究官
MATSUURAI Yoshiharu  OSAKA UNiV., DPT OF MEDICINE, PROFESSOR, 微生物病研究所, 教授
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywordshepatitis C virus / protein transduction / protease / transgenic mice / caspase
Research Abstract

Although interferon (IFN) therapy can eradicate hepatitis C virus (HCV) from chronic hepatitis C patients, the eradication rate, to date, is only 30%, which is not satisfactory. The most serious impediment in achieving eradication of HCV from patients lies in the difficulty to clear residual HCV in hepatocytes, or to eliminate HCV-infected hepatocytes.
To provide a novel method for eradicating HCV from patients, we conducted to establish an experimental system that utilizes the protein-transducting-domain (ptd) of the TAT protein from human immunodeficiency virus. Fusion proteins with the ptd can be distributed to all organs upon the injection of the proteins into the peritoneal cavity. By arranging the Caspase 3 protease subunits p17 and p12 intervened by the recognition sequences of HCV protease that is coded by the NS3 domain of HCV genome, we produced an efficient method to kill only hepatocytes infected with HCV ; HCV-infected hepatocytes possess the HCV protease that activates the Caspase 3, leading the hepatocytes into suicide.
By introducing the plasmid pTAT-Casp3-NS3pcs, which encodes the ptd-Caspase3 p17-NS3 cleavage site-p12-NS3 cleavage site, with an expression vector of HCV NS3 protease, HepG2 cells underwent apoptosis.
On the other hand, we established transgenic mouse lines carrying the cDNA for HCV NS2-NS5. mRNA transcribed from the NS2-NS5B genes was detected in the mouse liver. Using these mice, an experiment is underway of injecting the protein purified from baculovirus transfected with pTAT-Casp3-NS3pcs.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Koike K, et al.: "Role of hepatitis viruses in hepatocarcinogenesis"Oncology. 62. 29-37 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yotsuyanagi H, et al.: "Frequent presence of hepatitis B virus in the sera from HBs antigen-negative, anti-HBc-positive blood donors"Transfusion. 9. 1093-1099 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujie H, et al.: "Hepatitis B virus genotypes and hepatocellular carcinoma in Japan"Gastroenterology. 120. 1564-1565 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Moriya K, et al.: "Increase of carbon 18 mono-unsaturated fatty acids in the liver of hepatitis C : Analysis in transgenic mice and humans"Biophys Biochem Res Commun. 281. 1207-1212 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Moriya K, et al.: "Oxidative stress in the absence of inflammation in the liver of a mouse model or hepatitis C virus -associated hepatocellular carcinoma"Cancer Res. 61. 4365-4370 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujie H, et al.: "Frequent β-catenin aberration in human hepatocellular carcinoma"Hepatol Res. 20. 39-51 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koike K, Tsutsumi T, Fujie H, Shintani Y, Moriya K: "Role of hepatitis viruses in hepatocarcinogenesis"Oncology. 62. 29-37 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yotsuyanagi H, Yasuda K, Shintani Y, Moriya K, Fujie H, Tsutsumi T, Nojiri N, Juji T, Hoshino H, Shimoda K, Hino K, Iino S, Koike K: "Frequent presence of hepatitis B virus in the sera from HBs antigen-negative, anti-HBc-positive blood donors"Transfusion. 9. 1093-1099 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujie H, Moriya K, Shintani Y, Yotsuyanagi H, Iino S, Kimura S, Koike K: "Hepatitis B virus Genotypes and hepatocellular carcinoma in Japan"Gastroenterology. 120. 1564-1565 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Moriya K, Todoroki T, Tsutsumi T, Fujie H, Shintani Y, Miyoshi H, Ishibashi K, Takayama T, Makuuchi M, Watanabe K, Miyamura T, Kimura S, Koike K: "Increase of carbon 18 mono-unsaturated fatty acids in the liver of hepatitis C : Analysis in transgenic mice and humans"Biophys Biochem Res Commun. 281. 1207-1212 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Miyazawa T, Ishibashi K, Horie T, Imai K, Miyamura T, Kimura S, Koike K: "Oxidative stress in the absence of inflammation in the liver of a mouse model for hepatitis C virus -associated hepatoceliular carcinoma"Cancer Res. 61. 4365-4370 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujie H, Moriya K, Shintani Y, Tsutsumi T, Takayama T, Makuuchi M, Kimura S, Koike K: "Frequent β-catenin aberration in human hepatocellular carcinoma"Hepatol Res. 20. 39-51 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koike K, et al.: "Role of hepatitis viruses in hepatocarcinogenesis"Oncology. 62. 29-37 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yotsuyanagi H, et al.: "Frequent presence of hepatitis B virus in the sera from HBs antigen-negative, anti-HBc-positive blood donors"Transfusion. 9. 1093-1099 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujie H, et al.: "Hepatitis B virus genotypes and hepatocellular carcinoma in Japan"Gastroenterology. 120. 1564-1565 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Moriya K, et al.: "increase of carbon 18 mono-unsaturated fatty acids in the liver of hepatitis C : Analysis in transgenic mice and humans"Biophys Biochem Res Commun. 281. 1207-1212 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Moriya K, et al.: "Oxidative stress in the absence of inflammation in the liver of a mouse modelf or hepatitis C virus -associated hepatocellular carcinoma"Cancer Res. 61. 4365-4370 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujie H, et al.: "Frequent β-catenin aberration in human hepatocellular carcinoma"Hepatol Res. 20. 39-51 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shintani Y, et al.: "Significance of hepatitis B virus DNA detected in hepatocellular carcinoma in patients with hepatiits C."Cancer. 88. 2478-2486 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yotsuyanagi H, et al.: "Virological analysis of "non-B, non-C" hepatocellular carcinoma in Japan : frequent involvement of hepatitis B virus."J Infect Dis. 181. 1920-1928 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujie H, et al.: "Hepatitis B virus genotypes and hepatocellular carcinoma in Japan."Gastroenterology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Moriya K, et al.: "Increase of carbon 18 mono-unsaturated fatty acids in the liver of hepatitis C : Analysis in transgenic mice and humans."Biophys Biochem Res Commun. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Moriya K, et al.: "Oxidative stress in the absence of inflammation in the liver of a mouse model for hepatitis C virus-associated hepatocellular carcinoma."Cancer Res. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujie H, et al.: "Frequent β-catenin aberration in human hepatocelluar carcinoma."Hepatol Res. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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