siRNA Therapeutic Design: Tools and Challenges

Abstract

Current RNA-based therapeutics are principally focused toward activating the RNA interference (RNAi) pathway through exogenous administration of short interfering RNAs (siRNAs) and sometimes short hairpin RNAs (shRNAs). The promise of RNAi-based therapeutics arises from their broad applicability and excellent specificity. This chapter reviews siRNA design strategies for improving intracellular interactions with the RNAi pathway proteins as well as key characteristics required for the design of optimal delivery vehicles to maximize specific silencing in only the cells of interest. The status of previous and ongoing clinical trials will be described as these provide insight for overcoming future challenges for long-term use of RNAi as a therapeutic modality.