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FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver
Interdepartmental Biological Sciences Graduate Program, Northwestern University Evanston, IL 60208-3120, USA
Department of Chemical and Biological Engineering, Chemistry of Life Processes Institute, Member, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Evanston, IL 60208-3120, USA
* Author to whom correspondence should be addressed.
Received: 28 March 2013; in revised form: 10 April 2013 / Accepted: 24 April 2013 / Published: 29 April 2013
Abstract: Many aspects of intercellular communication are mediated through “sending” and “receiving” packets of information via the secretion and subsequent receptor-mediated detection of biomolecular species including cytokines, chemokines, and even metabolites. Recent evidence has now established a new modality of intercellular communication through which biomolecular species are exchanged between cells via extracellular lipid vesicles. A particularly important class of extracellular vesicles is exosomes, which is a term generally applied to biological nanovesicles ~30–200 nm in diameter. Exosomes form through invagination of endosomes to encapsulate cytoplasmic contents, and upon fusion of these multivesicular endosomes to the cell surface, exosomes are released to the extracellular space and transport mRNA, microRNA (miRNA) and proteins between cells. Importantly, exosome-mediated delivery of such cargo molecules results in functional modulation of the recipient cell, and such modulation is sufficiently potent to modulate disease processes in vivo. It is possible that such functional delivery of biomolecules indicates that exosomes utilize native mechanisms (e.g., for internalization and trafficking) that may be harnessed by using exosomes to deliver exogenous RNA for therapeutic applications. A complementary perspective is that understanding the mechanisms of exosome-mediated transport may provide opportunities for “reverse engineering” such mechanisms to improve the performance of synthetic delivery vehicles. In this review, we summarize recent progress in harnessing exosomes for therapeutic RNA delivery, discuss the potential for engineering exosomes to overcome delivery challenges and establish robust technology platforms, and describe both potential challenges and advantages of utilizing exosomes as RNA delivery vehicles.
Keywords: exosome; nanoparticle; siRNA delivery; extracellular vesicle; gene therapy; cancer; immunity
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MDPI and ACS Style
Marcus, M.E.; Leonard, J.N. FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver. Pharmaceuticals 2013, 6, 659-680.
Marcus ME, Leonard JN. FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver. Pharmaceuticals. 2013; 6(5):659-680.
Marcus, Michelle E.; Leonard, Joshua N. 2013. "FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver." Pharmaceuticals 6, no. 5: 659-680.