1998 Fiscal Year Final Research Report Summary
In vivo HVJ-liposome mediated gene transfer into intestine and carcinoma.
| Project/Area Number |
08457336
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | First Department of Surgery, Hyogo College of Medicine |
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Principal Investigator |
OKAMOTO Eizo Hyogo College of Medicine, First Department of Surgery, Professor, 医学部, 教授 (50068425)
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| 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)
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| Project Period (FY) |
1996 – 1998
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| Keywords | HVJ-liposome / Intestine / Cytokine / Inflammatory bowel disease / HGF |
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| 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.
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