Delivery of RNAi therapeutics: work in progress.

RNA interference (RNAi) therapeutics appear to offer substantial opportunities for future therapy. However, post-administration RNAi effectors are typically unable to reach disease target cells in vivo without the assistance of a delivery system or vector. The main focus of this review is on lipid-based nanoparticle (LNP) delivery systems in current research and development that have at least been shown to act as effective delivery systems for functional delivery of RNAi effectors to disease target cells in vivo. The potential utility of these LNP delivery systems is growing rapidly, and LNPs are emerging as the preferred synthetic delivery systems in preclinical studies and current nonviral RNAi effector clinical trials. Moreover, studies on LNP-mediated delivery in vivo are leading to the emergence of useful biophysical parameters and physical organic chemistry rules that provide a framework for understanding in vivo delivery behaviors and outcomes. These same parameters and rules should also suggest ways and means to develop next generations of LNPs with genuine utility and long-term clinical viability.