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Therapeutically harnessing extracellular vesicles

Abstract

The field of extracellular vesicle (EV) research has developed rapidly over the last decade from the study of fundamental biology to a subject of significant clinical relevance. The potential of harnessing EVs in the diagnosis and treatment of diseases — including cancer and neurological and cardiovascular disorders — is now being recognized. Accordingly, the applications of EVs as therapeutic targets, biomarkers, novel drug delivery agents and standalone therapeutics are being actively explored. This Review provides a brief overview of the characteristics and physiological functions of the various classes of EV, focusing on their association with disease and emerging strategies for their therapeutic exploitation.

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Fig. 1: Classes of EVs, their biogenesis and features and methods of isolating them.
Fig. 2: The role of EVs in cancer, neurodegenerative diseases and cardiovascular disease.
Fig. 3: Methods of therapeutically targeting EVs and producing therapeutic EVs.

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Acknowledgements

Research in the Hill lab is supported by grants from the National Health and Medical Research Council of Australia (to A.F.H. GNT1041413; GNT1132604), and the Australian Research Council (to A.F.H. DP170102312; DP190101655).

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Glossary

Extracellular vesicles

(EVs). Membranous particles secreted by mammalian and bacteria cells into the extracellular space.

Endosomal pathways

The uptake or internalization of proteins through the endocytic pathway, which largely involves the early/sorting endosome, late endosomes and multivesicular bodies.

Non-endosomal pathways

The uptake or internalization of proteins through the process of recruiting cargo into developing pits and subsequently forming vesicles.

Apoptotic bodies

A type of extracellular vesicles formed by cells undergoing apoptosis.

Microvesicles

Extracellular vesicles formed by outward blebbing of the plasma membrane of the cell.

Exosomes

A type of extracellular vesicles formed through an endocytic process and released through the multivesicular body.

Neurodegenerative diseases

A collective term for neurological diseases normally associated with ageing.

Endosomal sorting complex required for transport

(ESCRT). A family of proteins involved in the endocytic formation of small extracellular vesicles such as exosomes.

Multivesicular body

A cellular structure in which endosomally derived extracellular vesicles are formed and from which they are released.

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Cheng, L., Hill, A.F. Therapeutically harnessing extracellular vesicles. Nat Rev Drug Discov 21, 379–399 (2022). https://doi.org/10.1038/s41573-022-00410-w

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