Therapeutic application of RNA interference to suppress hepatitis C virus replication

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Small interfering RNAs (siRNAs) efficiently inhibit gene expression by RNA interference. Here, we report efficient inhibition, by both synthetic and vector-derived siRNAs, of hepatitis C virus (HCV) replication, as well as viral protein synthesis, using an HCV replicon system. The siRNAs were designed to target the 5' -untranslated region (5' -UTR) of the HCV genome, which has an internal ribosomal entry site for translation of the entire viral polyprotein. Moreover, 5' -UTR is the most conserved throughout the genome, making it an ideal target for siRNA. Importantly, we have identified a very effective site within 5' -UTRR, where ^〜80% suppression of HCV replication was achieved with concentrations of siRNA as low as 2.5 nM. Furthermore, DNA-based vectors expressing siRNA against HCV also were effective, which might allow efficient gene delivery of RNAi into hepatocytes in vivo using virus vectors. Taken together, our results support the feasibility of utilizing siRNA-based gene therapy to inhibit HCV replication, which may prove valuable in the therapy of hepatitis C.