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Identification of scaffold proteins for improved endogenous engineering of extracellular vesicles

Author

Listed:
  • Wenyi Zheng

    (Karolinska Institutet)

  • Julia Rädler

    (Karolinska Institutet)

  • Helena Sork

    (University of Tartu)

  • Zheyu Niu

    (Karolinska Institutet
    Shandong Provincial Hospital Affiliated to Shandong First Medical University)

  • Samantha Roudi

    (Karolinska Institutet)

  • Jeremy P. Bost

    (Karolinska Institutet)

  • André Görgens

    (Karolinska Institutet
    University Hospital Essen, University of Duisburg-Essen)

  • Ying Zhao

    (Karolinska Institutet
    Karolinska University Hospital)

  • Doste R. Mamand

    (Karolinska Institutet)

  • Xiuming Liang

    (Karolinska Institutet)

  • Oscar P. B. Wiklander

    (Karolinska Institutet)

  • Taavi Lehto

    (Karolinska Institutet
    University of Tartu)

  • Dhanu Gupta

    (Karolinska Institutet)

  • Joel Z. Nordin

    (Karolinska Institutet)

  • Samir EL Andaloussi

    (Karolinska Institutet)

Abstract

Extracellular vesicles (EVs) are gaining ground as next-generation drug delivery modalities. Genetic fusion of the protein of interest to a scaffold protein with high EV-sorting ability represents a robust cargo loading strategy. To address the paucity of such scaffold proteins, we leverage a simple and reliable assay that can distinguish intravesicular cargo proteins from surface- as well as non-vesicular proteins and compare the EV-sorting potential of 244 candidate proteins. We identify 24 proteins with conserved EV-sorting abilities across five types of producer cells. TSPAN2 and TSPAN3 emerge as lead candidates and outperform the well-studied CD63 scaffold. Importantly, these engineered EVs show promise as delivery vehicles in cell cultures and mice as demonstrated by efficient transfer of luminal cargo proteins as well as surface display of different functional entities. The discovery of these scaffolds provides a platform for EV-based engineering.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40453-0
    DOI: 10.1038/s41467-023-40453-0
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    References listed on IDEAS

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