Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment
| Autor: | Daniel Bojar, Marie Daoud El-Baba, Simon Ausländer, Ghislaine Charpin-El Hamri, Kelly R. Tan, Ryosuke Kojima, Giorgio Rizzi, Pratik Saxena, Martin Fussenegger |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell signaling Science General Physics and Astronomy Cell Communication Biology Exosomes Exosome General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Cytosol Drug Delivery Systems Cell Line Tumor microRNA Animals Humans RNA Messenger lcsh:Science 3' Untranslated Regions Cerebrum Neuroinflammation Messenger RNA Multidisciplinary Electroporation HEK 293 cells Brain Mesenchymal Stem Cells Parkinson Disease General Chemistry Genetic Therapy Catalase Microvesicles 3. Good health Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology HEK293 Cells Nanoparticles lcsh:Q Female Synthetic Biology 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) Nature Communications, 9 (1) |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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