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Therapeutic approach to hepatitis C using single-chain antibody and DNA gene transfer

Research Project

Project/Area Number 08557040
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

HAYASHI Norio  Osaka University Medical School, Professor, 医学部, 教授 (00144478)

Co-Investigator(Kenkyū-buntansha) HIRAMATSU Naoki  Osaka Univ.Hosp., Medical Staff, 医学部・附属病院, 医員
KASAHARA Akinori  Osaka Univ.Hosp., Associate Professor, 医学部・附属病院, 助教授 (70214286)
三田 英治  大阪大学, 医学部・付属病院, 医員
結城 暢一  大阪大学, 医学部・付属病院, 医員
竹原 徹郎  大阪大学, 医学部・附属病院, 医員
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1996: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsSingle-chain antibody / Hepatitis C virus / Hepatitis B virus / Virus particle / Packaging / HBc / Replicative intermediate / Hepatoma cell line / C型肝炎 / single-chain抗体 / DNAワクチン / 遺伝子治療 / HBc抗原 / 単鎖状体 / sFv
Research Abstract

A cDNA for single-chain antibody (sFv) against hepatitis B virus core protein (HBc), 1C9, was isolated. We also cloned a cDNA for control sFv (γ9) that could not react HBc. HB611 cells that carry three copies of HBV-DNA and produce HBV particles were transfected with 1C9 or γ9 and we established the HB611 cells that stably express 1C9 or γ9, respectively. We found no difference in production of each HBV transcript and protein between 1C9-expressing HB611 and γ9-expressing ones. However, expression of HBV replicative intermediate was inhibited in 1C9-expressing HB611 compared with γ9-expressing ones. These results suggested that sFv against HBc might inhibit the packaging of pregenome RNA into HBc particles. Thus sFv against viral capsid protein was shown to be useful for inhibition of encapsidation of viral genome and sFv against hepatitis C virus core protein may be a candidate for therapeutic application of hepatitis C.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Kuzushita N,et al.: "Involvement of transporter associated with antigen processing (TAP) 2 gene polymorphisms in hepatitis C virus infection."Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanto T,et al.: "Impaired allostimulatory capacity of peripheral blood dendritic cell recovered from hepatitis C virus-infected individuals."Journal of Immunology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takehara T,et al.: "Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice : hepatoprotective role of TNFα."Hepatology. 27. 1643-1651 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ito Y,et al.: "Activation of mitogen-activated protein kinase/extracellular signal-related kinases in human hepatocellular carcinoma."Hepatology. 27. 951-958 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuzushita N,et al.: "Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus."Hepatology. 27. 240-244 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iio S,et al.: "Serum levels of soluble Fas antigen in chronic hepatitis C."Journal of Hepatology. 29. 517-523 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuzushita N, et al.: "Involvement of transporter associated with antigen processing (TAP) 2 gene polymorphisms in hepatitis C virus infection"Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanto T, et al.: "Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals"J Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noda K ,et al.: "Gene expression of α1-6 fucosyltransferase in human hepatoma tissues A possible implication for increased fucosylation of α-fetoptotein"Hepatology. 28. 944-952 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takehara T, et al.: "Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice Hepatoprotective role of TNFα"Hepatology. 27. 1643-1651 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kasahara A, et al.: "Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C"Hepatology. 27. 1394-1402 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ito Y, et al.: "Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in human hepatocellular carcinoma"Hepatology. 27. 951-958 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuzushita N, et al.: "Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus"Hepatology. 27. 240-244 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iio S, et al.: "Serum levels of soluble Fas antigen in chronic hepatitis C patients"J. Hepatol. 29. 517-523 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oshita M, et al.: "GBV-C/HGV infection in chronic hepatitis C patients : Its effect on clinical features and interferon therapy"J Med Virol. 55. 98-102 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanto T, et al.: "Cross-linking of Fcγ-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T lymphocyte induction in vitro"Immunology. 94. 461-468 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noda K, et al.: "High expression of α1-6 fucosyltransferase during rat hepatocarcinogenesis"Int J Cancer. 75. 444-450 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka H, et al.: "Hepatitis C virus 1b (II) infection and development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma : a case-control study in Japan"J Epidemiol. 8. 244-249 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wada S, et al.: "Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth"J Gastrol Hepatol. 13. 635-642 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuzushita N,et al.: "Involvement of transporter associated with antigen processing(TAP)2 gene polymorphisms in hepatitis C virus infection." Gastroenterology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanto T,et al.: "Impaired Allostimulatory Capacity of Peripheral Blood Dendritic Cells Recovered from Hepatitis C Virus-Infected Individuals" Journal of Immunology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Takehara T,et al.: "Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice:hepatoprotective role of TNFα." Hepatology. 27. 1643-1651 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ito Y,et al.: "Activation of mitogen-activated protein kinase/extracellular signal-nelated kinases in human hepatocellular carcinoma." Hepatology. 27. 951-958 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuzushita N,et al.: "Influence of HLA haplotypes on the clinical courses of individuals in fected with hepatitis C virus." Hepatology. 27. 240-244 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iio S,et al.: "Serum levels of soluble Fas antigen in chromic hepatitis C." Journal of Hepatology. 29. 517-523 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuki N, et al.: "Relation of disease activity during chronic hepatitis C infection to complexity of hypervariable region 1 quasispecies." Hepatology. 25. 439-444 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mochizuki K.et al.: "B7.BB-1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C." Hepatology. 25. 713-718 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tatsumi T, et al.: "Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma." Hepatology. 25. 1108-1114 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuzushita N, et al.: "influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus." Hepatology. 27. 240-244 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kasahara A, et al.: "Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C" Hepatology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Takehara T, et al.: "Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice." Hepatology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Mochizuki K,et al.: "Fas antigen expression in liver tissues of patients with chronic hepatitis B." Journal of Hepatology. 24. 1-7 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuzushita N,et al.: "Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels." Journal of Medical Virology. 48. 1-7 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yuki N,et al.: "Hepatitis C biochemical remission and viral replication in haemodialysis patients." Journal of Medical Virology. 48. 242-246 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takehara T,et al.: "In vivo gene transfer and expression in rat stomach by submucosal injection of plasmid DNA." Human Gene Therapy. 7. 589-593 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ito Y,et al.: "Little expression of proto-oncogene bc1-2 in tumourous cells of hepatocellular carcinoma with chronic hepatitis C virus infection." International Hepatology Communications. 4. 316-325 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yuki N,et al.: "Quantitative analysis of antibody to hepatitis C virus envelope 2 glycoprotein in patients with chronic hepatitis C infection." Hepatology. 23. 947-952 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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