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

Author

Listed:
  • Ryosuke Kojima

    (Department of Biosystems Science and Engineering
    The University of Tokyo)

  • Daniel Bojar

    (Department of Biosystems Science and Engineering)

  • Giorgio Rizzi

    (University of Basel)

  • Ghislaine Charpin-El Hamri

    (Institut Universitaire de Technologie (IUTA))

  • Marie Daoud El-Baba

    (Institut Universitaire de Technologie (IUTA))

  • Pratik Saxena

    (Department of Biosystems Science and Engineering)

  • Simon Ausländer

    (Department of Biosystems Science and Engineering)

  • Kelly R. Tan

    (University of Basel)

  • Martin Fussenegger

    (Department of Biosystems Science and Engineering
    University of Basel)

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.

Suggested Citation

  • Ryosuke Kojima & Daniel Bojar & Giorgio Rizzi & Ghislaine Charpin-El Hamri & Marie Daoud El-Baba & Pratik Saxena & Simon Ausländer & Kelly R. Tan & Martin Fussenegger, 2018. "Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03733-8
    DOI: 10.1038/s41467-018-03733-8
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    Cited by:

    1. Justin A. Peruzzi & Taylor F. Gunnels & Hailey I. Edelstein & Peilong Lu & David Baker & Joshua N. Leonard & Neha P. Kamat, 2024. "Enhancing extracellular vesicle cargo loading and functional delivery by engineering protein-lipid interactions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Chi-Ling Chiang & Yifan Ma & Ya-Chin Hou & Junjie Pan & Sin-Yu Chen & Ming-Hsien Chien & Zhi-Xuan Zhang & Wei-Hsiang Hsu & Xinyu Wang & Jingjing Zhang & Hong Li & Lili Sun & Shannon Fallen & Inyoul Le, 2023. "Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Daniel Strebinger & Chris J. Frangieh & Mirco J. Friedrich & Guilhem Faure & Rhiannon K. Macrae & Feng Zhang, 2023. "Cell type-specific delivery by modular envelope design," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Wenyi Zheng & Julia Rädler & Helena Sork & Zheyu Niu & Samantha Roudi & Jeremy P. Bost & André Görgens & Ying Zhao & Doste R. Mamand & Xiuming Liang & Oscar P. B. Wiklander & Taavi Lehto & Dhanu Gupta, 2023. "Identification of scaffold proteins for improved endogenous engineering of extracellular vesicles," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Shiyan Dong & Xuan Liu & Ye Bi & Yifan Wang & Abin Antony & DaeYong Lee & Kristin Huntoon & Seongdong Jeong & Yifan Ma & Xuefeng Li & Weiye Deng & Benjamin R. Schrank & Adam J. Grippin & JongHoon Ha &, 2023. "Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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