Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges

J Biomed Sci. 2023 Oct 16;30(1):88. doi: 10.1186/s12929-023-00981-9.

Abstract

RNA has emerged as a revolutionary and important tool in the battle against emerging infectious diseases, with roles extending beyond its applications in vaccines, in which it is used in the response to the COVID-19 pandemic. Since their development in the 1990s, RNA interference (RNAi) therapeutics have demonstrated potential in reducing the expression of disease-associated genes. Nucleic acid-based therapeutics, including RNAi therapies, that degrade viral genomes and rapidly adapt to viral mutations, have emerged as alternative treatments. RNAi is a robust technique frequently employed to selectively suppress gene expression in a sequence-specific manner. The swift adaptability of nucleic acid-based therapeutics such as RNAi therapies endows them with a significant advantage over other antiviral medications. For example, small interfering RNAs (siRNAs) are produced on the basis of sequence complementarity to target and degrade viral RNA, a novel approach to combat viral infections. The precision of siRNAs in targeting and degrading viral RNA has led to the development of siRNA-based treatments for diverse diseases. However, despite the promising therapeutic benefits of siRNAs, several problems, including impaired long-term protein expression, siRNA instability, off-target effects, immunological responses, and drug resistance, have been considerable obstacles to the use of siRNA-based antiviral therapies. This review provides an encompassing summary of the siRNA-based therapeutic approaches against viruses while also addressing the obstacles that need to be overcome for their effective application. Furthermore, we present potential solutions to mitigate major challenges.

Keywords: Antiviral; RNA interference; Small interfering RNA; Therapeutic; Virus.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • COVID-19* / genetics
  • COVID-19* / therapy
  • Humans
  • Pandemics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • RNA, Viral
  • Viruses* / genetics
  • Viruses* / metabolism

Substances

  • RNA, Small Interfering
  • Antiviral Agents
  • RNA, Viral