Drug delivery systems for RNA therapeutics

Nat Rev Genet. 2022 May;23(5):265-280. doi: 10.1038/s41576-021-00439-4. Epub 2022 Jan 4.

Abstract

RNA-based gene therapy requires therapeutic RNA to function inside target cells without eliciting unwanted immune responses. RNA can be ferried into cells using non-viral drug delivery systems, which circumvent the limitations of viral delivery vectors. Here, we review the growing number of RNA therapeutic classes, their molecular mechanisms of action, and the design considerations for their respective delivery platforms. We describe polymer-based, lipid-based, and conjugate-based drug delivery systems, differentiating between those that passively and those that actively target specific cell types. Finally, we describe the path from preclinical drug delivery research to clinical approval, highlighting opportunities to improve the efficiency with which new drug delivery systems are discovered.

Publication types

  • Review

MeSH terms

  • Drug Delivery Systems*
  • Genetic Therapy*
  • Genetic Vectors
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering