THERAPY OF HEPADNAVIRUS INFECTION USING ANTISENSE OLIGONUCLEOTIDES

Chronic infection with the hepatitis B virus (HBV) is a major health p roblem worldwide. The only established therapy is alpha-interferon wit h an efficacy of only 30-40% in highly selected patients. Major theore tical problems of therapeutical strategies against hepadnaviral infect ions are the limited immune response and the presence of covalently cl osed HBV DNA in the nucleus. Many nucleoside analogues and inhibitors of viral reverse transcriptases were tested in vitro and in vivo with transient effects and often severe side effects. Molecular therapeutic strategies include antisense DNA/RNA and ribozymes. In vitro antisens e oligodeoxynucleotides could be shown to inhibit viral replication an d gene expression in human hepatoma cell lines. In vivo an antisense o ligodeoxynucleotide directed against the 5'-region of the preS gene of the duck hepatitis B virus inhibited the viral replication and gene e xpression in ducks. These results demonstrate the potential clinical u se of antisense DNA/RNA as antiviral therapeutics.