Identification of scaffold proteins for improved endogenous engineering of extracellular vesicles

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, Joel Z. Nordin and Samir EL Andaloussi ()
Additional contact information
Wenyi Zheng: Karolinska Institutet
Julia Rädler: Karolinska Institutet
Helena Sork: University of Tartu
Zheyu Niu: Karolinska Institutet
Samantha Roudi: Karolinska Institutet
Jeremy P. Bost: Karolinska Institutet
André Görgens: Karolinska Institutet
Ying Zhao: Karolinska Institutet
Doste R. Mamand: Karolinska Institutet
Xiuming Liang: Karolinska Institutet
Oscar P. B. Wiklander: Karolinska Institutet
Taavi Lehto: Karolinska Institutet
Dhanu Gupta: Karolinska Institutet
Joel Z. Nordin: Karolinska Institutet
Samir EL Andaloussi: Karolinska Institutet

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40453-0

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DOI: 10.1038/s41467-023-40453-0

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