siRNAs: a new wave of RNA-based therapeutics

Open Access
Publisher Website
Google Scholar
Abstract
In 1998, Fire et al.1 made the startling discovery that double-stranded RNA (dsRNA) could induce a potent silencing effect on homologous genes in the nematode Caenorhabditis elegans. This technique, termed RNA interference (RNAi), has proved to be a powerful tool with which to dissect gene function in plants, C. elegans and Drosophila. Although RNAi is evolutionarily conserved among plants and animals, silencing of specific genes in mammalian cells has been difficult because of the induction of the interferon response by dsRNAs of ≥30 nt.2,3 This non-specific response to dsRNA leads to global changes in cellular gene expression and apoptosis, masking any specific silencing effect by RNAi in mammalian cells. Recently, however, it was shown that potent and specific gene silencing could be achieved in human cells transfected with small interfering RNAs (siRNA) of 21–23 nt, a key intermediate in the RNAi pathway.4 This landmark discovery by Tuschl and co-workers has led to routine RNA interference in mammalian cell culture and may have finally opened the door to tractable genetic analysis in mammalian cells.

This publication has 0 references indexed in Scilit: