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Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment

Kojima, Ryosuke and Bojar, Daniel and Rizzi, Giorgio and Hamri, Ghislaine Charpin-El and El-Baba, Marie Daoud and Saxena, Pratik and Ausländer, Simon and Tan, Kelly R. and Fussenegger, Martin. (2018) Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment. Nature communications, 9 (1). p. 1305.

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Official URL: https://edoc.unibas.ch/65365/

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Abstract

Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Physiopathology of basal ganglia neuronal subcircuits (Tan)
UniBasel Contributors:Tan, Kelly and Rizzi, Giorgio
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Apr 2020 21:25
Deposited On:26 Apr 2020 21:25

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