Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications.

Extracellular vesicles (EVs) are membrane vesicles, the submicron-size microparticles and the nanometer-size exosomes, that carry RNAs, proteins and lipids from their parent cells. EV generation takes place under cellular activation or stress. Cells use EVs to communicate with other cells by delivering signals through their content and surface proteins. Beyond diagnostic and discovery applications, EVs are excellent candidates for enabling safe and potent cell and gene therapies, especially those requiring strong target specificity. Here we examine EVs, their engineering and applications by dissecting mechanistic and engineering aspects of their components that endow them with their unique capabilities: their cargo and membranes proteins. Both EV cargo and membranes can be independently engineered and used for various applications. We review early efforts for their biomanufacturing.