miRNA-122 from Laboratory biomarker to the treatment of HCV

Hepatitis C virus (HCV) is an important human pathogen that infects as many as 185 million persons worldwide, In the long-term, this can lead to advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma HCC, there is currently no vaccine for hepatitis C. About 15–45% of infected persons spontaneously clear the virus within 6 months of infection without any treatment, miRNAs are endogenous short single-stranded noncoding  RNAs and they are post-transcriptional negative regulators of gene expression, about18-22 nucleotides long, and play a crucial role in the regulation of gene expression. Now there are over 2500  mature potential human microRNAs recorded in miRBase (version 20, accessed January 2014), 84 miRNAs in serum and plasma of HCV-infected patients to identify miRNAs that correlated with different stages histologically assessed liver disease severity and during HCV infection, miRNA-122 is the most abundant in the liver,miRNA-122 is responsible^, for liver homeostasis, several studies showed that miRNA-122 is required for HCV replication in infected cells, it can use as a serum biomarker over alanine leucine transaminase(ALT) in predicting the presence of chronic HCV infection, miR-122 also plays a crucial role in the regulation of cholesterol and fatty acid metabolism in the adult liver, and was identified as a regulator for systematic iron homeostasis, therapies that target it could present an effective approach for the development of new HCV antiviral drugs, Recently, the development of the anti-miR122 therapeutic miravirsen. Miravirsen (formerly SPC3649) is a 15-base oligonucleotide that is complementary to part of miR-122 and is the first miRNA-targeting agent administered to patients. Miravirsen has demonstrated in vitro antiviral activity against all HCV genotypes, Miravirsen interferes with the functions of miR-122 both in viral proliferation and in cholesterol homeostasis, miravirsen has demonstrated broad antiviral activity and a relatively high genetic barrier to resistance.