Extracellular vesicles (EVs) are nanometer-sized, lipid membrane-enclosed vesicles secreted by most, if not all, cells and contain lipids, proteins, and various nucleic acid species of the source cell. EVs act as important mediators of intercellular communication that influence both physiological and pathological conditions. Given their ability to transfer bioactive components and surmount biological barriers, EVs are increasingly being explored as potential therapeutic agents. EVs can potentiate tissue regeneration, participate in immune modulation, and function as potential alternatives to stem cell therapy, and bioengineered EVs can act as delivery vehicles for therapeutic agents. Karolinska Institutet researchers discuss recent approaches and advances of EV-based therapies.
EV engineering and loading strategies
EVs can be loaded with therapeutic entities such as RNA species, proteins, and small-molecule drugs through exogenous loading (loading of isolated EVs) or endogenous loading (loading during EV biogenesis). The producer cell can further be engineered to express EVs displaying therapeutic proteins or targeting peptides via chimeric proteins consisting of an EV-sorting domain fused to the protein of interest. Similarly, RNA-binding proteins (RBPs) can be explored to bind therapeutic RNA. RNA aptamers or therapeutic RNA can also be attached to EVs by hydrophobic modifications.