Inhibition of Hepatitis B Virus Expression and Replication by Rna Interference

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Abstract
RNA interference (RNAi) is the process of sequence–specific gene silencing, initiated by double–stranded RNA (dsRNA) that is homologous in sequence to the target gene. Because it has been shown that RNAi can be accomplished in cultured mammalian cells by introducing small interfering RNAs (siRNAs), much effort has been invested in exploiting this phenomenon for experimental and therapeutic means. In this study, we present a series of experiments showing a significant reduction in hepatitis B virus (HBV) transcripts and proteins in cell culture, as well as in the viral replicative forms, induced by siRNA–producing vectors. The antiviral effect is sequence–specific and does not depend on active viral replication. In conclusion, our data suggest that RNAi may provide a powerful therapeutic tool, acting both on replication–competent and on replication–incompetent HBV. (Hepatology 2003;37:764–770.)