Nanomedicine-based delivery strategies for nucleic acid gene inhibitors in inflammatory diseases

Adv Drug Deliv Rev. 2021 Aug:175:113809. doi: 10.1016/j.addr.2021.05.019. Epub 2021 May 24.

Abstract

Thanks to their abilities to modulate the expression of virtually any genes, RNA therapeutics have attracted considerable research efforts. Among the strategies focusing on nucleic acid gene inhibitors, antisense oligonucleotides and small interfering RNAs have reached advanced clinical trial phases with several of them having recently been marketed. These successes were obtained by overcoming stability and cellular delivery issues using either chemically modified nucleic acids or nanoparticles. As nucleic acid gene inhibitors are promising strategies to treat inflammatory diseases, this review focuses on the barriers, from manufacturing issues to cellular/subcellular delivery, that still need to be overcome to deliver the nucleic acids to sites of inflammation other than the liver. Furthermore, key examples of applications in rheumatoid arthritis, inflammatory bowel, and lung diseases are presented as case studies of systemic, oral, and lung nucleic acid delivery.

Keywords: Gene inhibition; Inflammation; Nanoparticle; Nucleic acid.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use
  • Drug Delivery Systems / methods
  • Genes / drug effects
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Nanomedicine / methods*
  • Nanoparticle Drug Delivery System*
  • Nucleic Acids / administration & dosage*
  • Nucleic Acids / therapeutic use
  • Oligodeoxyribonucleotides, Antisense / administration & dosage
  • Oligodeoxyribonucleotides, Antisense / therapeutic use
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Nanoparticle Drug Delivery System
  • Nucleic Acids
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Small Interfering