Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment
Open accessAbstract
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.
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Engineered exosomes carrying RVG-Lamp2b can efficiently cross the blood-brain barrier and deliver catalase mRNA, resulting in a reduction of 6-OHDA-mediated neuroinflammation in a mouse model of Parkinson's disease.
“The designed exosome carrying RVG-Lamp2b was able to efficiently cross the blood–brain barrier (BBB) and deliver the catalase mRNA, resulting in a reduction of 6-OHDA-mediated neuroinflammation in a mouse model of Parkinson’s disease [101, 103].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [101]
EXOtic system carrying RVG-Lamp2b successfully crossed the BBB and delivered catalase mRNA.
“The developed system carrying RVG-Lamp2b successfully crossed the BBB and delivered catalase mRNA.”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [101]
This reduced neuroinflammation induced by 6-OHDA and neurotoxicity in a Parkinson's mouse model.
“This reduced neuroinflammation induced by 6-OHDA and neurotoxicity in a Parkinson's mouse model [101].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [101]
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- Authors
- Kojima, R., Bojar, D., Rizzi, G., Hamri, G. C.-E., El-Baba, M. D., Saxena, P., Ausländer, S., Tan, K. R., & Fussenegger, M.
- Affiliations
- ETH Zurich (CH)
- University of Basel (CH)
- Instituts Universitaires de Technologie (FR)
- Corresponding author
- Fussenegger, Martin
- ORCID
- Venue
- Nature Communications
- Published
- 2018-04-03
- Volume
- 9
- Issue
- 1
- Pages
- 1305-1305
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5880805
- OpenAlex
- W2795868806
- Cited by
- 748
- References
- 58
- Citations by year
- 2026: 77 · 2025: 101 · 2024: 130 · 2023: 128 · 2022: 113 · 2021: 84 · 2020: 60 · 2019: 44 · 2018: 9 · 2016: 1
- FWCI
- 17.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- ETH Zürich Research Collection (cc-by)
- Funders
- Karolinska Institutet
- FP7 Ideas: European Research Council (321381)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- exosome engineering, mRNA delivery, Parkinson's disease, catalase, cell-to-cell communication, neuroinflammation, neurotoxicity, RNA therapeutics
- MeSH terms
- Animals, Brain, Catalase, Cell Communication, Cytosol, Female, HeLa Cells, Humans, Mice, Inbred C57BL, Parkinson Disease, RNA, Messenger, Genetic Therapy, Drug Delivery Systems, Electroporation, 3' Untranslated Regions, MicroRNAs, Cell Line, Tumor, Mice, Nanoparticles, Cerebrum, Exosomes, HEK293 Cells, Synthetic Biology, Mesenchymal Stem Cells
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