Interfering with disease: a progress report on siRNA-based therapeutics.
RNA interference (RNAi) quietly crept into biological research in the 1990s when unexpected gene-silencing phenomena in plants and flatworms first perplexed scientists. Following the demonstration of RNAi in mammalian cells in 2001, it was quickly realized that this highly specific mechanism of sequence-specific gene silencing might be harnessed to develop a new class of drugs that interfere with disease-causing or disease-promoting genes. Here we discuss the considerations that go into developing RNAi-based therapeutics starting from in vitro lead design and identification, to in vivo pre-clinical drug delivery and testing. We conclude by reviewing the latest clinical experience with RNAi therapeutics.
de Fougerolles
Antonin
A
Alnylam Pharmaceuticals Inc., 300 Third Street, Cambridge, Massachusetts 02142, USA. tdefougerolles@alnylam.com
Vornlocher
Hans-Peter
HP
Maraganore
John
J
Lieberman
Judy
J
D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D008081:Liposomes; D011094:Polyethyleneimine / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use*
D008081:Liposomes; D011108:Polymers; D034741:RNA, Small Interfering; D011094:Polyethyleneimine