1995 Fiscal Year Final Research Report Summary
Development of treatment of Hepatitis B virus using transgenic (HBx gene) mice and cell lines by use of antisense DNA.
| Project/Area Number |
06807169
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
MATSUKURA Makoto Kumamoto University School of Medicine Department of Child Deveropment Assistant, 医学部, 助手 (70238997)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Transgenic mice / HBx gene / Antisense DNA / Inhibition of carcinogenesis |
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| Research Abstract |
While an important goal of treatment for hepatitis B is to prevent the development of hepatocellular carcinoma, there has been no effective therapy for it. Antisnese oligodeoxynucleotide treatment could in principle inhibit hepatitis B virus gene expression and suppress tumor development. We used a mouse model for hepatocellular carcinoma, which is trangenic for the hepatitits B virus HBx gene, to study antisnese phosphorothioate oligodeoxynucleotides. Among 2 series of sense and antisense oligodeoxynucleotides, only antisense sequence covering the initiation codon of the HBx gene effectively inhibited the expression of the HBx gene in the liver. Intraperitoneal administration of this antisense oligodeoxynucleotide three times a week for 8 weeks from 2 week old to 10 week old resulted in the prevention of preneoplastic lesion development in the liver without any adverse effect to the mice. Antisense phosphorothioate oligodeoxynucleotides may be a promising agent for the prevention of carcinogenesis in hepatitis B infection.
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