How do you get short RNAs into mammalian cells? The question has puzzled scientists since Andrew Fire and Craig Mello demonstrated the concept of RNAi in 1998. Short interfering (si)RNAs can jam the signals from specific genes, thus providing promise for exquisite genetic-based therapies. The challenges include aiming for the right mechanism without dragging other pathways into the fray, bypassing immune reactions, and simply getting past the cell membrane.













