title: In vivo inhibition of hepatitis B virus gene expression by antisense phosphorothioate oligonucleotides.
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. Antisense 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 transgenic for the hepatitis B virus HBx gene, to study antisense phosphorothioate oligodeoxynucleotides. Among 2 series of sense and antisense oligodeoxynucleotides, only antisense sequences covering the initiation codon of the HBx gene effectively inhibited the expression of the HBx gene in the liver. Intraperitoneal injection of this antisense oligodeoxynucleotide thrice a week for 8 weeks resulted in the prevention of preneoplastic lesion development in the liver without inflammation in the liver or developmental disturbance of the mice. Antisense phosphorothioate oligodeoxynucleotides can inhibit the expression of a hepatitis B virus gene and may be a promising method for the prevention of hepatocellular carcinoma in hepatitis B virus infection.
authors.affiliation: First Department of Internal Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Moriya
authors.forename: M
authors.initials: M
authors.lastname: Matsukura
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
authors.forename: K
authors.initials: K
authors.lastname: Koike
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control*; D013873:Thionucleotides
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides