Protein-based delivery systems for RNA delivery

J Control Release. 2023 Nov:363:253-274. doi: 10.1016/j.jconrel.2023.09.032. Epub 2023 Sep 28.

Abstract

RNA-based therapeutics have emerged as promising approaches to modulate gene expression and generate therapeutic proteins or antigens capable of inducing immune responses to treat a variety of diseases, such as infectious diseases, cancers, immunologic disorders, and genetic disorders. However, the efficient delivery of RNA molecules into cells poses significant challenges due to their large molecular weight, negative charge, and susceptibility to degradation by RNase enzymes. To overcome these obstacles, viral and non-viral vectors have been developed, including lipid nanoparticles, viral vectors, proteins, dendritic macromolecules, among others. Among these carriers, protein-based delivery systems have garnered considerable attention due to their potential to address specific issues associated with nanoparticle-based systems, such as liver accumulation and immunogenicity. This review provides an overview of currently marketed RNA drugs, underscores the significance of RNA delivery vector development, delineates the essential characteristics of an ideal RNA delivery vector, and introduces existing protein carriers for RNA delivery. By offering valuable insights, this review aims to serve as a reference for the future development of protein-based delivery vectors for RNA therapeutics.

Keywords: Delivery vectors; Protein carriers; RNA delivery challenges; RNA drug; RNA-based therapeutics.

Publication types

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

MeSH terms

  • Gene Transfer Techniques*
  • Genetic Vectors
  • Humans
  • Neoplasms* / therapy
  • RNA

Substances

  • RNA