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Infection with hepatitis C virus (HCV) is one of the major global health problems, approximately 170 million people are infected worldwide. The chronic HCV infection is associated with a high risk of developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Unfortunately, there is still no effective vaccine or antibodies available for the prevention of infection. RNA interference (RNAi) represents a promising new approach to combat viral infections, and recent developments in the field of gene therapy have increased the feasibility of clinical applications. RNAi techniques have made rapid progress in the basic understanding of HCV biology and revealed numerous new viral and host-cell factors as potential targets for therapy. Together with the improvement of gene delivery technique and the discovery of the critical role of microRNA (miRNA) in HCV infection, RNAi and miRNA-based antiviral strategies hold great promise for the future. In this article, we provide a comprehensive overview of current developments of therapeutic targets of RNAi, liver-targeted delivery systems and the potential applications of miRNAs in treatment of hepatitis C infection.
Genetic Therapy ; Hepacivirus ; genetics ; Hepatitis C ; therapy ; Humans ; MicroRNAs ; genetics ; RNA Interference

10.Effect of short interfering RNAs on hepatitis C Virus 5' untranslated region expression.

Zhao-jun CHEN ; La-hong ZHANG ; Wei LI ; Xia LIU

Chinese Journal of Experimental and Clinical Virology 2007;21(4):319-321

OBJECTIVETo evaluate interfering effect of several short interfering RNAs (siRNA) on HCV 5' untranslated region(5' UTR).

METHODSThe green fluorescent protein (GFP) was used as reporter gene. A fused gene of HCV-5'UTR and GFP was constructed. It was cloned into the plasmid pCDNA3.1 named as pcDNA-HCV-5'UTR-GFP. Three siRNAs were designed and transfected into HepG2 cells with pcDNA-HCV-5'UTR-GFP. The change of the fluorescence intensity of HepG2 cells was shown by fluorescence microscopy and numerically detected under 488 nm wave length by flow cytometry.

RESULTSThe fused gene of HCV-5'UTR and GFP was successfully constructed. The seven groups displayed inhibitory effects on the gene expression of GFP. The inhibition rates of siRNA A, B and C were 68.4 percent, 72.6 percent and 75.6 percent, respectively. The inhibitory rates of siRN A + B, siRN B +C and siRN A +C were 91.8 percent, 87.2 percent and 92.4 percent, respectively. The inhibitory rates of siRN A+B +C was the highest, up to 95.7 percent.

CONCLUSIONThese siRNAs could inhibit expression of HCV 5'UTR gene, the inhibitory effect of combined siRNA was better than that of single siRNAs.

5' Untranslated Regions ; genetics ; Green Fluorescent Proteins ; genetics ; Hepacivirus ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection

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10.Effect of short interfering RNAs on hepatitis C Virus 5' untranslated region expression.

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