Action and reaction: The biological response to sirna and its delivery vehicles

Abstract

RNA interference (RNAi)-based therapeutics have significant potential for the treatment of human disease. Safe and effective delivery of RNA to target tissues remains a major barrier to realizing its clinical potential. Several factors can affect the in vivo performance of short interfering RNA (siRNA) delivery formulations, including siRNA sequence, structure, chemical modification, and delivery formulation. This review provides an introduction to the principles underlying the pharmacokinetics and pharmacodynamics of systemically administered siRNA and its delivery formulations, including the factors that lead to its degradation, clearance, and tissue uptake, as well as its potential for immunogenicity, toxicity, and off-target effects within the body. © The American Society of Gene & Cell Therapy.