The Benefits of Sequestration

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Science  10 May 2013:
Vol. 340, Issue 6133, pp. 661
DOI: 10.1126/science.340.6133.661-a

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).

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