Antisense gets a grip on miR-122 in chimpanzees.

Innovations in antisense drug design have enhanced potency and selectivity, as demonstrated in a recent study by Lanford and colleagues, who treated hepatitis C virus (HCV)-infected chimpanzees with SPC3649. This compound is a second-generation antisense RNA molecule that is complementary to the microRNA miR-122, a major regulatory RNA in liver that fine-tunes the expression of over 100 cellular genes and enhances HCV replication. Serum concentrations of cholesterol and HCV RNA were reduced in chimpanzees treated with 12 weekly intravenous infusions of SPC3649, and no major side effects were noted, paving the way for clinical trials of SPC3649 and other antisense drugs directed against microRNAs. Potential therapeutic uses of SPC3649 include the treatment of HCV infection and liver cancer.