RNAi in adult mice

Small interference RNAs (siRNAs) have shown great potential as gene silencing reagents in a wide range of experimental systems. In the 4 July Nature, Anton McCaffrey and colleagues at the Stanford University School of Medicine report the use of siRNAs to inhibit transgene expression in adult mice and to target hepatitis C virus sequences in vivo (Nature 2002, 418:38-39).

They used a modified hydrodynamic transfection method to deliver naked siRNAs to the liver of adult mice. They then monitored expression of a firefly luciferase reporter transgene using whole-body imaging techniques. McCaffrey et al. report specific siRNA-mediated inhibition (around 80%) of luciferase expression. They also found that small-hairpin RNAs, transcribed in vivo from DNA templates, could induce gene silencing in mice.

When siRNA was directed against the NS5B (non-structural protein 5B, viral polymerase-encoding region) it was also effective, suggesting that RNAi-based strategies may be used therapeutically to target human pathogens.