2000 Fiscal Year Final Research Report Summary
The mechanism of liver cell damage in the patients with HCV and development of ne therap and vaci
| Project/Area Number |
09670581
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
TOKUSHIGE Katsutoshi Tokyo Women's Medical University, Institute of Gastroenterology Instructor, 医学部, 助手 (60188729)
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| Project Period (FY) |
1997 – 2000
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| Keywords | HCV / DNA vaccine / Antisense RNA |
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| Research Abstract |
Previous study of DNA-based immunization, HCV core DNA expression plasmid induced CTL and humoral response, however, not so strong. 1) To enhance the immunity to HCV, we coimmunized mice with HCV core DNA expression plasmid and DNA expression constructs encoding for mouse IL-2, IL-4 and GM-CSF.The CD4 inflammatory T cell response as well as CD8+ CTL activity were enhanced substantially after coimmunization with IL-2 and GM-CSF DNA expression constructs. 2) To enhance the immunity to HCV, several HBV-HCV chimeric constructs were prepared. These constructs enhanced the proliferate activity of T cells as well as the humoral immune response to HCV core protein. 3) We developed approaches antisense RNA to inhibit HCV RNA translation and HCV core protein expression. The translation of HCV RNAs was efficiently inhibited by antisense RNA in vitro. The specificity of this inhibition was confirmed using control target RNA sequence or nonrelevant antisense RNA constructs. Co-transfection studies demonstrated that antisense RNA inhibited HCV core-luciferase fusion protein expression by 41-57% in HuH-7 cells. These studies indicated that antisense RNA will find viral RNA target sequence and inhibit HCV RNA translation.
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