MOLECULAR THERAPEUTIC STRATEGIES IN HEPATITIS-B VIRUS-INFECTION

Chronic infection with the hepatitis B virus is a major health problem worldwide. The only established therapy is interferon-alpha, with an efficacy of only 30-40% in highly selected patients. Nucleoside analog ues do not show a significant clinical benefit. Molecular therapeutic strategies aimed at blocking gene expression include antisense DNA/RNA and ribozymes acting at the posttranscriptional level and triple heli x formation blocking at the transcriptional level. In vitro, antisense oligodeoxynucleotides inhibit viral replication and gene expression i n human hepatoma cell lines. In vivo, an antisense oligodeoxynucleotid e directed against the 5'-region of the pre-S gene of the duck hepatit is B virus inhibited viral replication and gene expression in ducks. I n vitro, ribozymes accurately cleave HBV substrate RNA. Triple helix f ormation is another very promising molecular approach. Results in hepa dnaviral infection are not yet available, however.