Extracellular vesicles (EVs), endogenous nanocarriers of proteins, lipids, and genetic material, have been harnessed as intrinsic delivery vectors for nucleic acid therapies. EVs are nanosized lipid bilayer bound vesicles released from most cell types responsible for delivery of functional biologic material to mediate intercellular communication and to modulate recipient cell phenotypes. Due to their innate biological role and composition, EVs possess several advantages as delivery vectors for nucleic acid based therapies including low immunogenicity and toxicity, high bioavailability, and ability to be engineered to enhance targeting to specific recipient cells in vivo. Researchers from the University of Georgia discuss the current understanding of the biological role of EVs as well as the advancements in loading EVs to deliver nucleic acid therapies. They discuss the current methods and associated challenges in loading EVs and the prospects of utilizing the inherent characteristics of EVs as a delivery vector of nucleic acid therapies for genetic disorders.
Schematic of EV biogenesis and contents
EVs are formed by the invagination of the early endosome to form the multivesicular body (MVB). In the MVB, the vesicles are coined intraluminal vesicles, and shuttled to be released by the plasma membrane. Once released, the ILVs are coined exosomes or generally extracellular vesicles. EV cargo consists of DNA, RNA, proteins, lipids. The EV membrane contains common tetraspanin proteins including CD9, CD63, and CD81.