Our bodies are made up of trillions of cells that work together to keep us alive. Key to their success is communication between cells in different parts of the body. Our cells have ingenious ways of overcoming the challenge of communicating across distances, with extracellularly secreted vesicles (EVs) as the key players.

All biological cells, including all eukaryotic and prokaryotic cells, release different EVs to communicate with their local external environments or with more distant tissues and organs. EVs released by cells carry and deliver unique cargo – proteins, lipids, and nucleic acids – from one cell to another, thereby inducing physiological changes in recipient cells, participating in several cellular processes, and affecting normal and pathological conditions. The EVs migrate to a neighboring cell or into the bloodstream, which can deliver them throughout the body. When the EVs are taken into the receiving cells, their cargo causes physiologic changes.

EVs are tiny, heterogeneous, membrane-covered droplets of different sizes, though all have diameters less than one-hundredth of a red blood cell. A collective term, “EV” covers various cell-released, membranous vesicle subtypes including exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many more. The intracellular or cell membrane origins of EVs remain subjects of debate.

The select repertoire of RNA and proteins carried via EVs reflects the physiological and pathological conditions of their cell of origin. Moreover, because they swiftly and efficiently transport biomolecules between cells, tissues and organs (e.g. across the blood-brain barrier), EVs are important mediators of disease propagation. EV research offers paradigm-shifting insight into how cancers systemically send out EV-drones to suppress the immune system and facilitate metastasis. As a result, EVs are useful circulating biomarkers for many cancers: liquid biopsy analyzing EV contents from blood allows us to monitor disease progression over time.

With efficient cellular uptake and delivery, lack of immunogenicity, and low toxicity, EVs are used as therapeutic agents and delivery vectors for treatment materials. Engineered EVs, or synthetic bionanovesicles built according to EV composition and structure, are now being employed to deliver genes, plasmids, proteins, RNA, and other biomaterials such as CRSPR/Cas9. Delivering viruses (AAVs) encapsulated in EVs can circumvent resistance by neutralizing antibodies, a major challenge in the field of gene therapy.

EV research has revolutionized our approach to understanding disease propagation, diagnosis, and therapeutics.