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Introduction
The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (1,2). An estimated 185 million people around the world are infected with HCV, with three to four million new cases each year (3). However, the pathogenesis of HCV remains to be fully elucidated. The standard of care (SOC) for HCV is the combined application of pegylated interferon α and ribavirin, with a sustained virological response (SVR) rate of up to 50%; however, the various genetic subtypes of HCV exhibit differing response rates to treatment (4). In addition, the treatment cost is high and there is a significant risk of side effects (5,6). The development of small molecule inhibitors targeting HCV replication-associated enzymes has recently achieved success in HCV therapy, with a significant increase in SVR (7–10). Despite this advance, the issue of resistance remains a problem (11,12), even when used in combination therapy with the SOC. Therefore, the development of novel antiviral strategies is required in order to more effectively treat HCV infection.
RNA interference (RNAi) is a post-transcriptional cellular process mediated by short (21–25 nucleotides) double-stranded RNA molecules (13), which are capable of gene silencing (14–17). MicroRNAs (miRNAs) are members of this group of small RNAs. The primary miRNAs are processed by the Drosha ribozyme and DGCR8 into precursor miRNAs consisting of 60–70 nucleotides (18). These miRNAs are subsequently exported from the nucleus by Exportin-5 (19), and processed into mature miRNAs by the ribonuclease-III enzyme Dicer (18). The guiding strand of the mature miRNA is then loaded into the RNA-induced silencing complex (20) to form the miRNA-containing ribonucleoprotein complex (miRNP), which is able to mediate the cleavage of target mRNA or result in translational repression (16). Artificial miRNAs (amiRNAs) comprise a class of artificially synthesized RNAs (21), similar to cellular miRNAs, which may be harnessed to silence mRNAs encoding pathogenic proteins for use in therapeutic strategies and functional genomics (22).
The HCV genome is a 9.6 kb positive-stranded RNA molecule containing a long open reading frame encoding a polyprotein precursor, which is processed by cellular and viral proteases into structural (Core, E1 and E2) and nonstructural (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) proteins. The HCV core protein is a conserved protein, which comprises the viral...