Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies

Gene. 2014 Apr 1;538(2):217-27. doi: 10.1016/j.gene.2013.12.019. Epub 2014 Jan 7.


During recent decades there have been remarkable advances in biology, in which one of the most important discoveries is RNA interference (RNAi). RNAi is a specific post-transcriptional regulatory pathway that can result in silencing gene functions. Efforts have been done to translate this new discovery into clinical applications for disease treatment. However, technical difficulties restrict the development of RNAi, including stability, off-target effects, immunostimulation and delivery problems. Researchers have attempted to surmount these barriers and improve the bioavailability and safety of RNAi-based therapeutics by optimizing the chemistry and structure of these molecules. This paper aimed to describe the principles of RNA interference, review the therapeutic potential in various diseases and discuss the new strategies for in vivo delivery of RNAi to overcome the challenges.

Keywords: Gene-silencing; RNA interference; RNAi delivery; Therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / therapy
  • Drug Delivery Systems
  • Gene Silencing*
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Genetic Therapy / trends
  • Genetic Vectors
  • HIV Infections / genetics
  • HIV Infections / therapy
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / therapy
  • Humans
  • Neoplasms / genetics
  • Neoplasms / therapy
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / therapy
  • RNA Interference* / immunology
  • RNA Stability
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use


  • RNA, Small Interfering