Delivering the promise of small ncRNA therapeutics

Abstract

Small non-coding RNA (ncRNA) therapeutics make use of small ncRNA effectors for desired therapeutic purposes that are essentially short (10–20 kD) RNA segments. These small ncRNA effectors are potentially tremendously powerful therapeutic agents, but 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 the use of lipid-based nanoparticles (LNPs) for the functional delivery of small ncRNA effectors in vivo. LNPs appear to be amongst the most effective delivery systems currently available for this purpose. 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 LNP-mediated 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.