The Benefits of Sequestration

Abstract

Biomedicine About 170 million people worldwide are infected with hepatitis virus (HCV), which causes progressive liver disease, and current antiviral therapies are only partially effective and/or cause adverse side effects. HCV survival and replication require binding of the viral genomic RNA to a noncoding RNA of host origin that is abundant in the liver, called miR-122. Therapies that lower miR-122 levels have been tested in preclinical models of HCV infection with encouraging results. Janssen et al. now report the results of a phase 2a clinical trial designed to assess the safety and efficacy of a chemically modified antisense oligonucleotide that sequesters miR-122 into a stable heteroduplex, thereby inhibiting its function. In a study of 27 HCV-infected patients receiving five weekly injections of the oligonucleotide, those receiving the highest dose showed a substantial decline in plasma HCV levels that persisted for about 15 weeks before rebounding. No significant side effects were observed and, as a bonus, a 25% reduction in plasma cholesterol levels was observed. N. Engl. J. Med. 368 , 1685 (2013).