RNA interference in biology and medicine.
First discovered in plants the nematode Caenorhabditis elegans, the production of small interfering RNAs (siRNAs) that bind to and induce the degradation of specific endogenous mRNAs is now recognized as a mechanism that is widely employed by eukaryotic cells to inhibit protein production at a post-transcriptional level. The endogenous siRNAs are typically 19- to 23-base double-stranded RNA oligonucleotides, produced from much larger RNAs that upon binding to target mRNAs recruit RNases to a protein complex that degrades the targeted mRNA. Methods for expressing siRNAs in cells in culture and in vivo using viral vectors, and for transfecting cells with synthetic siRNAs, have been developed and are being used to establish the functions of specific proteins in various cell types and organisms. RNA interference methods provide several major advantages over prior methods (antisense DNA or antibody-based techniques) for suppressing gene expression. Recent preclinical studies suggest that RNA interference technology holds promise for the treatment of various diseases. Pharmacologists have long dreamed of the ability to selectively antagonize or eliminate the function of individual proteins--RNAi technology may eventually make that dream a reality.
Milhavet
Ollivier
O
Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Gary
Devin S
DS
Mattson
Mark P
MP
D000818:Animals; D016923:Cell Death; D004358:Drug Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy; D010600:Pharmacology / Q000639:trends*; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends