Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection

TLDR

MicroRNAs regulate cellular processes, and the highly conserved miR‑122 is essential for hepatitis C virus replication, yet current HCV therapies are limited by side effects and low efficacy. The study aimed to evaluate whether silencing miR‑122 could serve as a therapeutic strategy against HCV infection. They used a locked nucleic acid (LNA) oligonucleotide complementary to miR‑122 to inhibit its activity. In chimpanzees, LNA‑mediated miR‑122 silencing produced sustained symptom reduction and did not select for resistant viral strains.

Abstract

Anti-MicroRNA Antiviral MicroRNAs (miRNAs) are small noncoding RNAs found in eukaryotes and viruses. They are critical regulators of a wide range of cellular processes. The highly conserved miRNA miR-122 is required for infection by hepatitis C virus (HCV), a leading cause of liver disease in humans. Present HCV treatment regimes can have serious side effects and are effective in only 50% of cases. In order to try to tackle HCV infection, Lanford et al. (p. 198 , published online 3 December) targeted miR-122 using a complementary locked nucleic acid (LNA) oligonucleotide. Treatment of chimpanzees infected by HCV with the LNA antagonist resulted in a long-term reduction of disease symptoms without the concomitant appearance of resistant strains of the virus.