Expanding the toolbox of exosome-based modulators of cell functions


Posted: 2021-09-17 19:00:00
Biomaterials . 2021 Sep 12;277:121129. doi: 10.1016/j.biomaterials.2021.121129. Online ahead of print. Affiliations Expand Affiliations 1 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA. 2 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA; Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, 90089, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA; Research Center for Liver Diseases, University of Southern California, Los Angeles, CA, 90089, USA. Electronic address: yongz@usc.edu. Item in Clipboard Qinqin Cheng et al. Biomaterials. 2021. Show details Display options Display options Format Biomaterials . 2021 Sep 12;277:121129. doi: 10.1016/j.biomaterials.2021.121129. Online ahead of print. Affiliations 1 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA. 2 Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA; Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, 90089, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA; Research Center for Liver Diseases, University of Southern California, Los Angeles, CA, 90089, USA. Electronic address: yongz@usc.edu. Item in Clipboard Full text links CiteDisplay options Display options Format Abstract Exosomes are cell-derived extracellular vesicles and play important roles in mediating intercellular communications. Due to their unique advantages in transporting a variety of biomolecules, exosomes have been emerging as a new class of nanocarriers with great potential for therapeutic applications. Despite advancements in loading chemotherapeutics and interfering RNAs into exosomes, active incorporation of protein molecules into exosomes remains challenging owing to their distinctive physicochemical properties and/or a lack of knowledge of cargo sorting during exosome biogenesis. Here we report the generation of a novel type of engineered exosomes with actively incorporated membrane proteins or soluble protein cargos, named genetically infused functionally tailored exosomes (GIFTed-Exos). Through genetic fusion with exosome-associated tetraspanin CD9, transmembrane protein CD70 and glucocorticoid-induced tumor necrosis factor receptor family-related ligand (GITRL) could be displayed on exosome surface, resulting in GIFTed-Exos with excellent T-cell co-stimulatory activities. By genetically linking to a CD9-photocleavable protein fusion, fluorescent protein mCherry, apoptosis-inducing protein apoptin, and antioxidant enzyme catalase could be effectively packed into exosomes for light-controlled release. The generated GIFTed-Exos display notable in vitro and in vivo activities for delivering distinct types of protein cargos to target cells. As a possibly general approach, GIFTed-Exos provide new opportunities to create exosomes with new functions and properties for biomedical research. Keywords: Drug delivery; Exosomes; Nanotechnology; Protein engineering; Synthetic biology. Copyright © 2021 Elsevier Ltd. All rights reserved. LinkOut - more resources Full Text Sources [x] Cite Copy Format: Send To [x]

参考サイト PubMed: exsome



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