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Development of Fiber-Mutant Adenovirus Vectors for targeting gene therapy

Research Project

Project/Area Number 13672282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionOsaka University

Principal Investigator

NAKAGAWA Shinsaku  Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (70207728)

Co-Investigator(Kenkyū-buntansha) TSUTSUMI Yasuo  Osaka University, Graduate School of Pharmaceutical Sciences, Research Associate, 薬学研究科, 助手 (50263306)
TADANORI Mayumi  Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (00098485)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsgene therapy / adenovirus vectors / targeting / RGD / CAR / integrins / dendritic cells / phage libraries / メラノーマ細胞
Research Abstract

We have demonstrated the usefulness of dendritic cells (DCs) genetically modified by adenovirus vectors (Ad) to immunotherapy, while sufficient gene transduction into DCs is required for high doses of Ad. The RT-PCR analysis revealed that the relative resistance of DCs to Ad-mediated gene transfer is due to the absence of Coxsackie-adenovirus receptor expression, and that DCs expressed adequate alpha(v)-integrins. Therefore, we investigated whether fiber-mutant Ad containing the Arg-Gly-Asp (RGD) sequence in the fiber knob can efficiently transduce and express high levels of the LacZ gene into DCs. The gene delivery by fiber-mutant Ad was more efficient than that by conventional Ad in both murine DC lines and normal human DCs (NHDC). Furthermore, NHDC transduced with fiber-mutant Ad and conventional Ad at 8000-vector particles/cell resulted in a 70-fold difference in beta-galactosidase activity. We propose that alpha(v)-integrin-targeted Ad is a very powerful tool with which to implement DC-based vaccination strategies.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Y.Okada: "Tumor Necrosis Factor alfa-Gene Therapy for an Established Murine Melanoma Using RGD (Arg-Gly-Asp) Fiber-mutant Adenovirus Vectors"Jpn. J. Cncer Res.. 93. 436-444 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Okada: "Fiber-mutant technique can augment gene transduction efficacy and anti-tumor effects against established murine melanoma by cytokine-gene therapy using adenovirus vectors"Cancer Letter. 1777. 57-63 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.OKADA: "Efficient Antigen Gene Transduction Using Arg-Gly-Asp Fiber-Mutant Adenovirus Vectors Can Potentiate Antitumor Vaccine Efficacy and Maturation of Murine Dendritic Cells"Cancer Res.. 61・21. 7913-7919 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.OKADA: "Efficient gene delivery into dendritic cells by fiber-mutant adenovirus vectors"Biochem. Biophys. Res. Commun.. 282. 173-179 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.NAKAGAWA: "Tetracycline-regulatable adenovirus vectors : pharmacologic properties and clinical potential"Eur. J. Pharm. Sci.. 13. 53-60 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Okada et al.: "Tumor Necrosis Factor alfa-Gene Therapy for an Established Murine Melanoma Using RGD (Arg-Gly-Asp) Fiber-mutant Adenovirus Vectors"Jpn. J. Oncer Res.. 93. 436-444 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Okada et al.: "Fiber-mutant technique can augment gene transduction efficacy and anti-tumor effects against established murine melanoma by cytokine-gene therapy using adenovirus vectors"Cancer Letter. 1777. 57-63 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Okada et al.: "Efficient Antigen Gene Transduction Using Arg-Gly-Asp Fiber-Mutant Adenovirus Vectors Can Potentiate Antitumor Vaccine Efficacy and Maturation of Murine Dendritic Cells"Cancer Res.. 61. 7913-7919 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Okada et al.: "Efficient gene delivery into dendritic cells by fiber-mutant adenovirus vectors"Biochem. Biophys. Res. Commun.. 282. 173-179 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Nakagawa et al.: "Tetracycline-regulatable adenovirus vectors: pharmacologic properties and clinical potential"Eur. J. Pharm. Sci.. 13. 53-60 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Okada: "Tumor Necrosis Factor alfa-Gene Therapy for an Established Miurine Melanoma Using RGD (Arg-Gly-Asp) Fiber-mutant Adenovirus Vectors"Jpn. J. Cncer Res.. 93. 436-444 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Okada: "Fiber-mutant technique can augment gene transduction efficacy and anti-tumor effects against established murine melanoma by cytokine-gene therapy using adenovirus vectors"Cancer Letter.. 1777. 57-63 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Nakagawa: "Tetracycline-regulatable adenovirus vectors : pharmacologic properties and clinical potential"Eur. J. Pharm. Sci.. 13. 53-60 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Okada: "Efficient gene delivery into dendritic cells by fiber-mutant adenovirus vectors"Biochem. Biophys. Res. Commun.. 282. 173-179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Okada: "Efficient Antigen Gene Transduction Using Arg-Gly-Asp Fiber-Mutant Adenovirus Vectors Can Potentiate Antitumor Vaccine Efficacy and Maturation of Murine Dendritic Cells"Cancer Res.. 61(21). 7913-7919 (2001)

    • Related Report
      2001 Annual Research Report

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

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