RNA interference in the clinic: challenges and future directions

Abstract

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. Although exploitation of RNAi has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release.

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

“…However, RNA interference mechanisms also confront several challenges that hinder their clinical translation. For instance, the cellular uptake of siRNA is limited due to its poor membrane permeability, and in general, siRNAs are also prone to rapid degradation by nucleases [35]. Although commercially available transfection agents effectively protect and deliver siRNA in vitro, they have limited clinical utility because of their inherent toxicities.…”

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

“…Since synthetic siRNA can be designed to target nearly any human gene, RNAi has become the method of choice to suppress gene expression for therapeutic purposes. Over the last decade, several excellent reviews have been published on the concept of RNAi [1][2][3] and its clinical potential [4,5]. Different target tissues and modes of administration have already been evaluated for siRNA, but most successes to date have emerged from local delivery.…”

RNAi-based Knockdown of Multidrug Resistance-associated Protein 1 is Sufficient to Reverse Multidrug Resistance of Human Lung Cells

“…The potent and fundamental gene-silencing mechanism of RNAi is to generate considerable excitement in the fields of molecular biology and gene therapy, but delivery is probably the biggest obstacle to the development of RNAi-based therapeutic agents (Xiao et al, 2008;Pecot et al, 2011). Vector-based delivery of shRNA could improve the efficiency of siRNA delivery which can obtain the stable expression of shRNAs using strong RNA polymerse-III promoters like U6 or H1 (Miyagishi et al, 2002;Ansaloni et al, 2010).…”