SiRNA Mediated Gene Silencing: Hurdles, Strategies and Applications

Abstract

Background: RNA interference (RNAi) has emerged as one of the most extensively explored areas of research that has promising applications in therapeutics. As an endogenous regulatory pathway, RNAi can be used for silencing targeted genes involved in the progression of diseases. Small interfering RNAs (siRNA) are 21-25 nucleotides in length and work on the principle of RNA interference. Owing to their high degree of safety, specificity, efficacy, easy synthesis and unrestricted choice of target, siRNAs are considered appropriate for gene silencing. Objective: This review discusses siRNA gene silencing mechanism, the challenges posed in siRNA delivery and the strategies developed to overcome some of these hurdles using nanocarriers. A few applications of siRNA in therapeutics are presented to highlight the utility of these strategies. Conclusion: In spite of advantages of siRNA technology, several shortcomings such as off-target effects, hurdles in delivering, endosomal trapping, stimulation of immune response and short half-life limit the practical use of siRNA. However, the situation has been improved considerably using nanotechnology based tools. Keywords: Nanocarriers, RNA interference, siRNA, challenges, delivery strategies, non-viral vectors.