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

  • Kojima R ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland.
  • Bojar D ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland.
  • Rizzi G Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
  • Hamri GC Département Génie Biologique, Institut Universitaire de Technologie (IUTA), F-69622, Villeurbanne Cedex, France.
  • El-Baba MD Département Génie Biologique, Institut Universitaire de Technologie (IUTA), F-69622, Villeurbanne Cedex, France.
  • Saxena P ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland.
  • Ausländer S ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland.
  • Tan KR Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
  • Fussenegger M ETH Zürich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058, Basel, Switzerland. martin.fussenegger@bsse.ethz.ch.
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  • 2018-04-04
Published in:
  • Nature communications. - 2018
3' Untranslated Regions
Animals
Brain
Catalase
Cell Communication
Cell Line, Tumor
Cerebrum
Cytosol
Drug Delivery Systems
Electroporation
Exosomes
Female
Genetic Therapy
HEK293 Cells
HeLa Cells
Humans
Mesenchymal Stem Cells
Mice
Mice, Inbred C57BL
MicroRNAs
Nanoparticles
Parkinson Disease
RNA, Messenger
Synthetic Biology
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/52368
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