Reprogramming Exosomes for Biomedical Applications

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Abstract Exosomes are extracellular vesicles secreted by many types of cells and play important roles in mediating intercellular communications. Endogenous exosomes have been emerging as a new and attractive class of therapeutics, owing to their unique and important characteristics. However, effective approaches remain limited for targeting exosomes to desired cells and tissues. And few methods are available for active loading of protein cargos into exosomes for cellular delivery. To address these challenges for broadening therapeutic utility of exosomes and unleashing their full potential, we propose to develop an innovative platform technology, termed synthetic multivalent antibodies retargeted exosomes (SMART-Exos). This will be achieved through genetically and chemically engineering exosomes with functional antibodies, ligands, and enzymes, combined with encapsulation of different types of therapeutic payloads. By integrating knowledge and technologies in exosome biology, protein engineering, synthetic chemistry, and enzyme inhibitor design, we aim to design and generate a series of SMART-Exos with new and/or enhanced functions and properties through distinct but complementary strategies. The resulting SMART-Exos are expected to redirect exosomes toward target cells in high specificity for modulating cellular functions and processes through receptor engagement and/or cargo delivery, leading to the development of a general and versatile platform technology for next-generation investigational and therapeutic exosomes.