Use of Artificial microRNAs for Gene Silencing
Betty Mowa and Abdullah Ely
from: Applied RNAi: From Fundamental Research to Therapeutic Applications (Edited by: Patrick Arbuthnot and Marc S. Weinberg). Caister Academic Press, U.K. (2014)
The discovery of the RNA interference (RNAi) pathway in 1998 resulted in intense excitement and interest in elucidating the mechanisms of this gene regulatory pathway. These studies laid the groundwork for manipulating the RNAi pathway to silence genes of interest in functional genomics studies and for therapeutic purposes. Mammalian RNAi is mainly activated by non-coding double stranded RNA molecules called microRNAs (miRNAs). Induction of RNAi can be achieved with exogenous RNA molecules that mimic the various intermediates of the pathway. This review discusses application of RNAi intermediate mimics for therapeutic gene silencing in mammalian cells. Like any other drug development strategy, using gene silencing as a therapeutic approach has not been without challenges. The most daunting of which include off-targeting effects, toxicity and identifying effective delivery vehicles. Intense dedication to overcome these problems has led to the approval of antisense based drugs for clinical use and progression of many more gene silencing lead candidates to clinical trials. The same dedication will see the use of artificial miRNAs in clinical settings read more ...