Therapeutic potential of engineered extracellular vesicles

Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of “cell-free, cell therapy” for cancer, immune disorders, and more recently cardiovascular disease. In addition, their unique properties of stability, biocompatibility, and low immunogenicity have prompted research into their potential as therapeutic delivery agents for drugs and small molecules. Researchers at University of Buffalo aim to provide a comprehensive overview of the current understanding of extracellular vesicle biology as well as engineering strategies in play to improve their therapeutic potential.

Biogenesis of EVs: exosomes, microvesicles and apoptotic bodies

a Exosomes originate from a double invagination of the plasma membrane. Their formation at endosomes is heavily dependent on ESCRT machinery. nSMase2 and members of the RAB GTPase family play different ESCRT-independent roles in exosome biogenesis. a modified from Robbins et al. b Microvesicles are derived from budding of the plasma membrane, controlled by regulatory and cytoskeletal proteins. Their membrane is comprised of homogenously distributed phosphatidylserine (PS) and phosphatidylethanolamine (PE). c Apoptosis results in the formation of apoptotic bodies. These vesicles are irregular in size and shape and contain nuclear fractions and cytoplasmic organelles along with extensive amounts of phosphatidylserine in their membrane. MVB, multivesicular bodies; Ub, ubiquitin