A comprehensive update of siRNA delivery design strategies for targeted and effective gene silencing in gene therapy and other applications

Expert Opin Drug Discov. 2023 Feb;18(2):149-161. doi: 10.1080/17460441.2022.2155630. Epub 2022 Dec 17.

Abstract

Introduction: RNA interference (RNAi) using small interfering RNA (siRNA) is a promising strategy to control many genetic disorders by targeting the mRNA of underlying genes and degrade it. However, the delivery of siRNA to targeted organs is highly restricted by several intracellular and extracellular barriers.

Areas covered: This review discusses various design strategies developed to overcome siRNA delivery obstacles. The applied techniques involve chemical modification, bioconjugation to specific ligands, and carrier-mediated strategies. Nanotechnology-based systems like liposomes, niosomes, solid lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (PNs) are also discussed.

Expert opinion: Although the mechanism of siRNA as a gene silencer is well-established, only a few products are available as therapeutics. There is a great need to develop and establish siRNA delivery systems that protects siRNAs and delivers them efficiently to the desired sitesare efficient and capable of targeted delivery. Several diseases are reported to be controlled by siRNA at their early stages. However, their targeted delivery is a daunting challenge.

Keywords: Small interfering RNA (siRNA); bioconjugation; chemical modification; drug delivery; gene delivery; gene silencing; gene therapy; nanotechnology; targeted gene delivery.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Silencing*
  • Genetic Therapy / methods
  • Humans
  • Nanoparticles*
  • Nanotechnology / methods
  • RNA Interference
  • RNA, Small Interfering

Substances

  • RNA, Small Interfering