Fig. 5.
MicroRNA miR-122 in hepatitis C virus (HCV) infection. After infection of a hepatocyte with the HCV, miR-122 promotes virus replication via different mechanisms. In contrast to the typical location of the microRNA binding in the 3 prime untranslated region (3′ UTR) of the target mRNA, miR-122 binds in the 5 prime untranslated region (5′UTR) of its target gene, the HCV mRNA. Opposite to target gene repression via binding to the 3′UTR, miR-122 binding in the 5′ UTR and recruiting RNA-induced silencing complex (RISC) stimulate viral protein translation and stabilize the viral mRNA thereby promoting the propagation of HCV. SPC 3649 (Miravirsen), a locked nucleic acid oligonucleotide that binds to and sequesters miR-122, results in functional miR-122 inhibition. A study with 36 patients with chronic HCV genotype 1 infection who received five weekly subcutaneous injections of SPC 3649 resulted in prolonged dose-dependent reductions in HCV RNA levels. The patients received doses of 3, 5, or 7 mg/kg of body weight or placebo subcutaneously over a 29-day period and had been followed until 18 weeks after randomization. The study revealed no evidence of viral resistance or dose-limiting side effects.103