An antisense oligonucleotide that targets miR-122 reduces hepatitis C virus (HCV) replication in patients with chronic HCV type 1 infection (N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1209026).

miR-122 contributes to the propagation of HCV by binding two sites in an untranslated region of the viral genome, protecting it from degradation. Harry Janssen et al. carried out a phase 2a clinical trial of miravirsen, a phosphorothioate antisense oligonucleotide that strongly binds and sequesters miR-122.

Thirty-six patients with chronic HCV type 1 infection were randomized to receive five weekly subcutaneous injections of miravirsen at doses ranging from 3 to 7 mg per kilogram of body weight over a month and were subsequently followed for 18 weeks.

The treatment resulted in a dose-dependent reduction in HCV RNA levels that lasted beyond administration of the oligonucleotide. Importantly, there were no serious adverse effects of miravirsen and no evidence of viral resistance, highlighting the strong therapeutic potential of this approach.