MicroRNA-122 response element (miR-122 RE) (miR-122 RE)

MicroRNA-122 (miR-122) response elements are specific nucleotide sequences located within the 5' untranslated region (UTR) of the Hepatitis C Virus (HCV) genome (Jopling et al., 2005, Science). Unlike the typical role of microRNAs in suppressing gene expression, miR-122 binding to these viral response elements is essential for the stability and replication of the HCV RNA (Machlin et al., 2011, PNAS). This interaction protects the viral RNA from exonucleolytic degradation by host enzymes such as Xrn1 and facilitates the assembly of the viral translation complex (Li et al., 2013, PNAS). Because miR-122 is highly expressed in the liver and is a critical host factor for HCV, these response elements represent a unique therapeutic vulnerability. Drugs like Miravirsen (SPC3649) and RG-101 are antisense oligonucleotides designed to sequester miR-122, thereby preventing its interaction with the viral response elements and effectively suppressing viral load (Janssen et al., 2013, NEJM). This approach provides a high barrier to resistance compared to traditional direct-acting antivirals because it targets a conserved host-virus interaction. Clinical studies have demonstrated that targeting this interaction leads to prolonged suppression of viremia in patients with chronic HCV infection. However, since miR-122 also regulates host genes involved in cholesterol metabolism, its sequestration can lead to a reversible decrease in serum cholesterol levels (Rothenberg et al., 2013, Journal of Hepatology).

Other names

miR-122 binding siteHCV 5' UTR miR-122 sitemiR-122 target siteHepatitis C virus miR-122 response element

Sequestration of host microRNA-122 by antisense oligonucleotides to prevent its binding to viral response elements, thereby promoting viral RNA degradation and inhibiting replication.