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Pre-clinical study of gene therapy against refractory diseases in animals.

Research Project

Project/Area Number 13460140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

OHNO Koichi  THE UNIVERSITY OF TOKYO, The University of Tokyo Graduate School of Agricultural and Life Sciences, Associate Professor (90294660)

Co-Investigator(Kenkyū-buntansha) TSUJIMOTO Hajime  東京大学, Graduate School of Agricultural and Life Sciences, Professor (60163804)
MASUDA Kenichi  東京大学, Graduate School of Agricultural and Life Sciences, Assistant (40313077)
IWATA Akira  財団法人日本生物科学研究所, Nippon Institute for Biological Science, Project-Leader (Researcher) (70193745)
長谷川 篤彦  東京大学, 大学院・農学生命科学研究科, 助教授 (90011923)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥17,500,000 (Direct Cost: ¥17,500,000)
Fiscal Year 2002: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2001: ¥9,100,000 (Direct Cost: ¥9,100,000)
Keywordsdogs / cats / gene therapy / Hepatocyte growth factor / tumor / adenovirus / feline immunodeficiency virus / アデノウイルスベクター / p53 / MDM2 / 肝細胞増殖因子(HGF)
Research Abstract

The object of this study is the development of gene therapy against tumors and immune-abnormalities in veterinary field. In this research period, the study of 1) basic research of gene therapy by hepatocyte growth factor (HGF), 2) construction of adenovirus vector containing canine p53 and its effects for canine tumor cell lines, 3) gene therapy for and by feline immunodeficiency virus (FIV), have been conducted.
1) HGF-gene therapy for liver and renal insufficiency in dogs and cats : Feline and canine HGF cDNA were cloned and their expressions were examined in various liver diseases in dogs together with tumor transforming growth factor (TGF). Furthermore, feline and canine HGF cDNA was inserted into expression plasmid and their efficient gene delivery method was examined.
2) Gene therapy for tumors in dogs and cats : Aberrations of the p53 tumor suppressor gene in various tumors in dogs was investigated together with the abnormalities of centrosome. We next constructed adenovirus vector expressing canine p53 which was cloned in our laboratory and examined its cytocidal effects on canine tumor cell lines. Furthermore, feline IL-18 cDNA was cloned and expression plasmid for canine CTLA-4 fusion protein to enhance anti-tumor immunity.
3) Gene therapy for FIV infection : We developed the novel method to quantify FIV RNA in plasma and an association of plasma viral RNA load with prognosis in cats naturally infected with FIV was investigated. We also investigated the mechanism of apoptosis of FIV-infected cells and cloned feline TNF receptors. Furthermore, feline vascular endotherial growth factor (VEGF) cDNA was cloned to develop new gene therapy against FIV infection.

Report

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

    (21 results)

All 2003 2002 2001 Other

All Journal Article (9 results) Publications (12 results)

  • [Journal Article] Molecular cloning of feline tumour necrosis factor receptor type I (TNFR I) and exp I and TNFR II in Iymphoid cells in cats.2003

    • Author(s)
      Mizuno, T., et al.
    • Journal Title

      European Journal of Immunogenetics 30

      Pages: 107-113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Effect of an adenoviral vector that expresses the canine p53 gene on cell growth of canine osteosarcoma and mammary adenocarcinoma cell lines.2003

    • Author(s)
      Yazawa, M., et al.
    • Journal Title

      American Journal of Veterinary Research (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Molecular cloning of feline tumour necrosis factor receptor type I (TNFR I) and expression of TNFR I and TNFR II in lymphoid cells in cats.2003

    • Author(s)
      Mizuno, T., et al.
    • Journal Title

      European Journal of Immunogenetics 30

      Pages: 107-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Association of plasma viral RNA load with prognosis in cats naturally infected with feline immunodeficiency virus.2002

    • Author(s)
      Goto, Y., et al.
    • Journal Title

      Journal of Virology 76

      Pages: 10079-10083

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Aberrations of the p53 tumor suppressor gene in various tumors in dogs.2001

    • Author(s)
      Setoguchi, A., et al.
    • Journal Title

      American Journal of Veterinary Research 62

      Pages: 433-439

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Telomere length and telomerase activity in canine mammary gland tumors.2001

    • Author(s)
      Yazawa, M., et al.
    • Journal Title

      American Journal of Veterinary Research 62

      Pages: 1539-1543

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Molecular cloning of feline hepatocyte growth factor (HGF)cDNA.2001

    • Author(s)
      Kobayashi, Y., et al.
    • Journal Title

      Journal of Veterinary Medical Science 63

      Pages: 211-214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Molecular cloning of feline hepatocyte growth factor (HGF) cDNA.2001

    • Author(s)
      Kobayashi, Y., et al.
    • Journal Title

      Journal of Veterinary Medical Science 63

      Pages: 211-214

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Effect of an adenoviral vector that expresses the canine p53 gene on cell growth of canine osteosarcoma and mammary adenocarcinoma cell lines.

    • Author(s)
      Yazawa, M., et al.
    • Journal Title

      American Journal of Veterinary Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Setoguchi, A.: "Aberration of the p53 tumor suppressor gene in various tumors in dogs"Am. J. Vet. Res.. 62. 433-439 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Setoguchi, A.: "Results of hyperamplification of centrosomes in naturally developing tumors of dogs"Am. J. Vet. Res.. 62. 1134-1141 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yazawa, M.: "Telomere length and telomerase activity in canine mammary gland tumors"Am. J. Vet. Res.. 62. 1539-1543 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanaya, N.: "Detection of the anti-P53 antibodies in a dog with tumor"J. Vet. Med. Sci.. 64. 973-979 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koga, L.: "Nucleotide sequence and expression of the feline vascular endotherial growth factor"J. Vet. Med. Sci.. 64. 453-456 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yazawa, M.: "An adenoviral vector expressing canine p53 inhibits cell growth of canine osteosarcoma adenocarcinoma cell lines"Am. J. Vet. Res.. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okai, Y. et al.: "Molecular analysis of multidrug resistance in lymphoma cells in the cat"Am.J.Vet.Res. 61. 1122-1127 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi, Y. et al.: "Molecular cloning of feline hepatocyte growth factor(HGF)cDNA"J.Vet.Med.Sci.. 63. 211-214 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Setoguchi, A. et al.: "Aberration of the p53 tumor suppressor gene in various tumors in dogs"Am.J.Vet.Res.. 62. 433-439 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yazawa, M. et al.: "Telomere length and telomerase activity in canine mammary gland tumors"Am.J.Vet.Res.. 62. 1539-1543 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maeda, S. et al.: "Molecular cloning of canine thymus and activation-regulated chemokine(TARC)gene an various tissues"J.Vet.Med.Sci.. 63. 1635-1638 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, A. et al.: "Molecular cloning and expression of the cDNA encoding feline granulocyte colony-stimulating factor"Gene. 274. 263-269 (2001)

    • Related Report
      2001 Annual Research Report

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

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