Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment
By Ryosuke Kojima, Daniel Bojar, G. Rizzi, Ghislaine Charpin-El Hamri, Marie Daoud El-Baba, Pratik Saxena, Simon Ausländer, Kelly R. Tan, M. Fussenegger. Nature Communications, 2018
638 citations recorded by the source corpus.
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. Exosomes function as intercellular information transmitters and are candidates for delivery of therapeutic agents. Here the authors present EXOtic, a synthetic biology device for in-situ production of designer exosomes and demonstrate in vivo application in models of Parkinson's disease.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f4f16dbe9fc79085327aedcf18271db97b51f6f3
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- Adelina-Gabriela Niculescu
- Crina Ioana Radu
- B. Costachescu
- D. Teleanu
- R. Teleanu
- O. Vladâcenco
- I. Lungu
- A. Grumezescu
Citations in the corpus
- An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases (2022, background): “Catalase treatment was reported to ameliorate memory deficit in AD [84], attenuate neurotoxicity and neuroinflammation [85], and provide significant neuroprotective effects in PD [86].”