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Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading

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Abstract

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. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

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Abbreviations

AAV:

Adeno-associated virus

CNS:

Central nervous system

DC:

Dendritic cells

EV:

Extracellular vesicle

hnRNPA2B1:

Heterogeneous nuclear riboprotein A2B1

Htt:

Huntingtin gene

iPSCs:

Induced pluripotent stem cells

MSC:

Mesenchymal stem cells

MVB:

Multivesicular body

OMVs:

Outer membrane vesicles

TAMEL:

Targeted and modular EV loading

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by the NIH UH2-UH3 award (1UH2TR000914-01) to T.D.S and M.A.P.

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Authors and Affiliations

  1. Division of Pharmaceutics and Pharmaceutical Sciences, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA

    Dhruvitkumar S. Sutaria, Mohamed Badawi & Mitch A. Phelps

  2. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA

    Dhruvitkumar S. Sutaria & Thomas D. Schmittgen

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  1. Dhruvitkumar S. Sutaria
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  2. Mohamed Badawi
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  3. Mitch A. Phelps
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  4. Thomas D. Schmittgen
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Correspondence to Thomas D. Schmittgen.

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Sutaria, D.S., Badawi, M., Phelps, M.A. et al. Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading. Pharm Res 34, 1053–1066 (2017). https://doi.org/10.1007/s11095-017-2123-5

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  • DOI: https://doi.org/10.1007/s11095-017-2123-5

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