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In vivo HVJ-liposome mediated gene transfer into intestine and carcinoma.

Research Project

Project/Area Number 08457336
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionFirst Department of Surgery, Hyogo College of Medicine

Principal Investigator

OKAMOTO Eizo  Hyogo College of Medicine, First Department of Surgery, Professor, 医学部, 教授 (50068425)

Co-Investigator(Kenkyū-buntansha) HABU Syusaku  Assistant Professor, 医学部, 助手 (00258154)
TAKEUCHI Masaharu  Assistant Professor, 医学部, 助手 (00258162)
NAKAI Yosiyuki  Assistant Professor, 医学部, 講師 (50198024)
FUJIMOTO Jiro  Assistant Professor, 医学部, 講師 (90199373)
TOYOSAKA Akihiro  Associated Professor, 医学部, 助教授 (20068498)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsHVJ-liposome / Intestine / Cytokine / Inflammatory bowel disease / HGF / HVJ リポソーム / 消化官 / HVJリボゾーム
Research Abstract

Several transfection methods have been developed to deliver exogenous genes into gastro-intestinal tract in vivo, but all have limitations. We evaluated the ability of Hemagglutmating virus of Japan (HVJ)-liposome mediated gene transfer to be used for gene therapy of incurrable intestinal diseases.
We first investigated the possibilities of HVJ-liposome mediated gene trasfere in vivo. Fluorescent isothiocyanate (FTTC )-labeled oligodeoxynucleotides (ODN) and Escherichia Coli beta -galactosidase (beta-gal) gene was introduced into rat intestine by HVJ-liposome in vivo to examine transfer efficacy throughtwo approaches ; one was delivered via mesenteric artery and the other was intraluminal delivery after preparation with Pronase to remove mucus barrier, In the both method the localization of FITC-Labeled ODN and expression of beta-gal gene was observed not only in intestinal lamina propria but also muscle layer of the rat intestine. Our results demonstrate that HVJ-liposome method is useful for introduction of foreign gene into intestinal tract. Furthermore we established the model of hapten (TNB) induced chronic colitis as a target site of gene therapy, which mimic human inflammatory bowel disease (IBD). Prior to gene therapy, we analyzed various cytokines such as IL-12, IL-18, TNF-alpha, INF-gamma and determined role of cytokine in this model utilizing IL- 18 knock out mouse and neutralization antibody for IL- 18. We conclude that in this model TNF-alpha and INF-gamma seems to play a major role of inducing chronic colitis. To investigate possibilities of HVJ-liposome mediated gene therapy against inflammatory bowel disease we trasfer HGF in this model and it result in decreasing colitis. For the future study we are estabished a model of radiation colitis utilizing for gene thrapy.

Report

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

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Hirano, T: "Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome" Gene Therapy. 5. 459-464 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, T: "HVJ-liposome mediated gene transfer into hepatocytes invivo" Journal of Hepatology. 29. 910-914 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, T: "Invivo HVJ-liposome mediated gene transfer into adult rat liver" Jpn.J.Gastroenterol Surg. 30(4). 906-909 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueki, T: "Hepatocyte growth factor gene therapy of liver cirrhosis in rats" Nature Medicine. 5(2). 226-230 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, T.: "Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome." Gene Therapy. 5. 459-464 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, T.: "HVJ-liposome mediated gene transfer into hepatocytes invivo." Journal of Hepatology. 29. 910-614 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano, T.: "Invivo HVJ-liposome mediated gene transfer into adult rat liver." Jpn.J.Gastroenterol Surg. 30 (4). 906-909 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueki, T.: "Hepatocyte growth factor gene therapy of liver cirrhosis in rats." Nature medicine. 5, (2). 226-230 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirano,T: "Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome" Gene Therapy. 5. 459-464 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirano,T: "HVJ-liposome mediated gene transfer into hepatocytes invivo" Journal of Hepatology. 29. 910-914 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirano,T: "Invivo HVJ-liposome mediated gene transfer into adult rat liver" Jpn.J.Gastroenterol surg. 30(4). 906-909 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueki,T: "Hepatocyte growth factor gene therapy of liver cirrhosis in rats" Nature Medicine. 5(2). 226-230 (1998)

    • Related Report
      1998 Annual Research Report

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

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