Exogenous loading of extracellular vesicles, virus-like particles, and lentiviral vectors with supercharged proteins

Exogenous loading of extracellular vesicles, virus-like particles, and lentiviral vectors with supercharged proteins

Cell membrane-based biovesicles (BVs) are important candidate drug delivery vehicles and comprise extracellular vesicles, virus-like particles, and lentiviral vectors. Here, we introduce a non-enzymatic assembly of purified BVs, supercharged proteins, and plasmid DNA called pDNA-scBVs. This multicom...

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Bibliographic Details
Published in:Communications biology Vol. 5; no. 1; p. 485
Main Authors: Breyne, Koen, Ughetto, Stefano, Rufino-Ramos, David, Mahjoum, Shadi, Grandell, Emily A., de Almeida, Luís P., Breakefield, Xandra O.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 19-05-2022
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Biology
Biomedical and Life Sciences
Cell culture
Cell membranes
Deoxyribonucleic acid
DNA
Drug delivery
Extracellular vesicles
Life Sciences
Membrane proteins
Neostriatum
Proteins
Virus-like particles
Viruses
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Summary:Cell membrane-based biovesicles (BVs) are important candidate drug delivery vehicles and comprise extracellular vesicles, virus-like particles, and lentiviral vectors. Here, we introduce a non-enzymatic assembly of purified BVs, supercharged proteins, and plasmid DNA called pDNA-scBVs. This multicomponent vehicle results from the interaction of negative sugar moieties on BVs and supercharged proteins that contain positively charged amino acids on their surface to enhance their affinity for pDNA. pDNA-scBVs were demonstrated to mediate floxed reporter activation in culture by delivering a Cre transgene. We introduced pDNA-scBVs containing both a CRE-encoding plasmid and a BV-packaged floxed reporter into the brains of Ai9 mice. Successful delivery of both payloads by pDNA-scBVs was confirmed with reporter signal in the striatal brain region. Overall, we developed a more efficient method to load isolated BVs with cargo that functionally modified recipient cells. Augmenting the natural properties of BVs opens avenues for adoptive extracellular interventions using therapeutic loaded cargo. The development of positive supercharged protein loading of cell membrane-based biovesicles, including extracellular vesicles, virus-like particles, and lentiviral vectors, as a strategy to deliver exogenous plasmid DNA to target cells in vitro and in vivo is presented.
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ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-022-03440-7