Achieving the Promise of Therapeutic Extracellular Vesicles

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading.

Different approaches to load EV therapeutics


EVs could be therapeutically loaded using endogenous and exogenous loading techniques. The endogenous approach involves overexpressing therapeutic cargo within the donor cells, which eventually gets loaded within the EVs. The exogenous approach includes the loading of therapeutic cargo within EVs once they are isolated. Depending upon the specific loading technique through which the cargo is loaded inside of the EVs, they could be further sub-classified into active and passive loading.

Sutaria DS, Badawi M, Phelps MA, Schmittgen TD. (2017) Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading. Pharm Res [Epub ahead of print]. [abstract]

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