5'-end of the HCV genome, in combination with functional experiments, suggests that the viral RNA has evolved to maximize protection from cytoplasmic exoribonucleases by altering the molecular behavior of Ago2. Another miRISC component, the DEAD-box RNA helicase DDX6, does not play a role in miR-122-facilitated HCV replication. The existing HCV therapy of PEG-IFNα plus ribavirin is poorly tolerated and frequently ineffective, so there is an urgent need for new drugs, and miR-122 inhibitors are an attractive possibility. The association between low miR-122 levels and hepatocellular carcinoma suggests that caution will be necessary when testing miR-122 inhibitors, and that long-term treatment might be undesirable. However, miR-122 is a promising target as it can be very selectively and effectively inhibited with antisense oligonucleotides, and as it is a conserved host factor it is hoped that the virus would not be able to acquire resistance mutations to an anti-miR-122 therapeutic. Moreover, engineering HepG2 cells to express miR-122 (HepG2-HFL cell, HepG2 cells expressing miR-122) mount an effective antiviral interferon-lambda (IFNλ) based innate immune response to hepatitis C virus (HCV) infection. HepG2 cells (stably expressing miR-122) produced a more robust IFN Response (type I and type III interferons) when challenged with other RNA viruses [ IAV-ΔNS1 and SeV ] and viral mimetics than Huh-7 and Huh-7.5 cells. HCV Induces an IFN-λ (IL28 and IL29), ISG, and Cytokine Response in these HepG2 cells with stably expressing miR-122. Inhibitor miravirsen As of 2017, Santaris Pharma was developing miravirsen, a locked nucleic acid-based antisense oligonucleotide that inhibits miR-122, as a potential treatment for HepC. Use as a biomarker miR-122 has recently been explored as a potential biomarker for various hepatic conditions. A change in levels of miR-122 in the blood has been confirmed as an indicator for viral-, alcohol- and chemical-induced liver injury as well as Transplant rejection after Liver transplantation. This change is noted before increased amino-transferase activity, making it an early indicator of liver disease and hepatocellular injury of liver grafts prior to liver transplantation. There is a great deal of research into the use of miR-122 as a biomarker for hepatitis C. While some studies dispute its efficacy for diagnosing Hep C, other research indicates that it may be useful in diagnosing specific forms of hepatitis. In addition, decreased levels of miR-122 in liver biopsies have been linked to a strain of hepatitis C that is resistant to interferon therapy. miR-122 has also been suggested