Drug delivery systems for RNA therapeutics

• Type of Material: Article
• Authors: Kalina Paunovska, Emory University; David Loughrey, Emory University; James Dahlman, Emory University
• Language: English
• Date: 2022-01-04
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © Springer Nature Limited 2022
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41576-021-00439-4
• Title of Journal or Parent Work: NATURE REVIEWS GENETICS
• Volume: 23
• Issue: 5
• Start Page: 265
• End Page: 280
• Keywords: ANTISENSE OLIGONUCLEOTIDES; IN-VIVO; LIPID-LIKE NANOPARTICLES; Genetics & Heredity; MODIFIED MESSENGER-RNA; Science & Technology; NORMAL ORGAN WEIGHTS; MOLECULAR-MECHANISMS; Life Sciences & Biomedicine; II-THE-BRAIN; POLYMERIC NANOPARTICLES; SIRNA DELIVERY; CHRONIC HEPATITIS-C
• Research Categories: Engineering, Biomedical

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.