Nucleic acid delivery with extracellular vesicles

Extracellular vesicles (EVs) are membrane-enclosed particles, heterogeneous in size, shape, contents, biogenesis and structure. They are released by eukaryotic and prokaryotic cells and exert (patho-)physiological roles as mediators for transmitting molecular information from the producer (donor) to a recipient cell. This review focuses on the potential of EVs for delivering nucleic acids, as particularly problematic cargoes with regard to stability/protection and uptake efficacy. It highlights important properties of EVs for nucleic acid delivery and discusses their physiological and pathophysiological roles with regard to various cellular RNA species. It then describes the application of EVs for delivering a broad selection of nucleic acids/oligonucleotides, in particular giving a comprehensive overview of preclinical in vivo studies and the various strategies explored. In this context, different techniques for EV loading are discussed, as well as other important technical aspects related to EV preparation, characterization and in particular, the various approaches of artificial EV modification.