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.
In dealing with living organisms, researchers had to start at the membrane. "Our main concern was the difficulty of getting highly charged nucleic acid inside the cell to reach the protein with the targeted activity," says Martin Woodle of Intradigm based in Rockville, Md.
Amid a rapid succession of discoveries, this issue's Hot Papers demonstrated distinct ways to package and ship siRNAs to specific cell targets. Both approaches allowed discrete siRNA delivery and silencing via intravenous injection in mice. In 2004, ...
