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Therapeutics


endorsed the use of the generic term extracellular vesicles (EV) for particles naturally released from the cell, delimited by a lipid bilayer and without a functional replicating nucleus3. It was highlighted that unless specific methods


can be used to reliably establish the origin of EVs, scientists should stay clear of using popular terms such as exosomes or microvesicles, as these can present contradictory or inaccurate definitions. These guidelines aim to unify the denomination of EV subtypes according to their physical character- istics, including: density or size (small EVs <200nm, or medium/large EVs), their biochemical composition (tetraspanins CD63+/CD81+- EVs, Annexin A5-stained EVs, etc) and cell of origin (eg podocyte EVs, hypoxic EVs, large oncosomes, apoptotic bodies, multivesicular bodies).


EVs as a novel class of biotherapeutics EVs can cross biological barriers, such as the blood-brain barrier, and get internalised into cells with a high degree of specificity. A growing body


Drug Discovery World Winter 2019/20


of evidence highlights their critical role in cell-to- cell communication pathways2. The natural prop- erties of EVs enable their forward engineering and further refinement to make EVs carrying specific drug candidates to target specific molecular path- ways, cells and tissues. Additionally, EVs are believed to evade the immune system, which opens new possibilities when approaching therapy devel- opment for a broad range of diseases. In recent years the number of EV-related publi-


cations has increased, with a study reporting an approximate increase of 733-fold in the past nine years4 – a trajectory analogous to that of fields such as T-cell research and circulating tumour cells. EV-related patents (UTSPO’s database) have also increased over the past decade, with a total of 524 US patents citing exosome-related terms between 2000-16. In the same period, a total of 948 NIH grants cited exosome(s) and/or microvesicle(s), with a 201% increase in 20164. Advances in EV research and technologies are driving the increased interactions between the


Figure 1 The potential of EVs in diagnostics and drug delivery. Schematic illustrating the role of EVs as small long-distance signalling units travelling around the human body and their therapeutic potential. EV cargoes reflect the cell of origin releasing the EV, and show distinctive composition in pathological conditions, making EVs appealing for early disease diagnostics and biomarker development tools, and the use of EVs for targeted drug delivery into tissues of interest


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