Mechanisms and functions of large extracellular vesicle biogenesis

Owing to the ability of extracellular vesicles (EVs) to encapsulate and transfer biomolecules for intercellular communication, EVs are recognized as promising candidates as biomarkers and therapeutic delivery vehicles. Small EVs (S-EVs), below 200 nm in diameter, have previously been the major focus in the EV field, but large EVs (L-EVs) are gaining considerable interest, with many distinct subsets of L-EVs having been described in the past few years. Here we review L-EV biogenesis from a context-specific perspective, focusing on the biological settings that drive L-EV formation. We also discuss the roles of L-EVs in facilitating the removal of unwanted cellular content and intercellular communication. Finally, we identify key challenges in the L-EV field and discuss future investigations towards harnessing L-EVs for diagnostic and therapeutic applications.