Illuminating RNA trafficking and functional delivery by extracellular vesicles

RNA-based therapeutics are highly promising for the treatment of numerous diseases, by their ability to tackle the genetic origin in multiple possible ways. RNA molecules are, however, incapable of crossing cell membranes, hence a safe and efficient delivery vehicle is pivotal. Extracellular vesicles (EVs) are endogenously derived nano-sized particles and possess several characteristics which make them excellent candidates as therapeutic RNA delivery agent. This includes the inherent capability to functionally transfer RNAs in a selective manner and an enhanced safety profile compared to synthetic particles. Nonetheless, the fundamental mechanisms underlying this selective inter-and intracellular trafficking and functional transfer of RNAs by EVs are poorly understood. Improving our understanding of these systems is a key element of working towards an EV-based or EV-mimicking system for the functional delivery of therapeutic RNA. In this review, state-of-the-art approaches to detect and visualize RNA in situ and in live cells are discussed, as well as strategies to assess functional RNA transfer, highlighting their potential in studying EV-RNA trafficking mechanisms. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This article discusses the potential of RNA-based therapeutics and the characteristics of extracellular vesicles as delivery agents, emphasizing the importance of improving understanding of EV-RNA trafficking mechanisms.