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Trafficking of JC virus-like particles across the blood–brain barrier

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Abstract

Hollow viral vectors, such as John Cunningham virus-like particles (JC VLPs), provide a unique opportunity to deliver drug cargo into targeted cells and tissue. Current understanding of the entry of JC virus in brain cells has remained insufficient. In particular, interaction of JC VLPs with the blood–brain barrier (BBB) has not been analyzed in detail. Thus, JC VLPs were produced in this study for investigating the trafficking across the BBB. We performed a carotid artery injection procedure for mouse brain to qualitatively study JC VLPs' in vivo binding and distribution and used in vitro approaches to analyze their uptake and export kinetics in brain endothelial cells. Our results show that clathrin-dependent mechanisms contributed to the entry of VLPs into brain endothelial cells, and exocytosis or transcytosis of VLPs across the BBB was observed in vitro. VLPs were found to interact with sialic acid glycans in mouse brain endothelia. The ability of JC VLPs to cross the BBB can be useful in developing a delivery system for transport of genes and small molecule cargoes to the brain.

Graphical abstract: Trafficking of JC virus-like particles across the blood–brain barrier

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Article information


Submitted
21 Oct 2020
Accepted
01 Feb 2021
First published
09 Feb 2021

This article is Open Access

Nanoscale Adv., 2021, Advance Article
Article type
Paper

Trafficking of JC virus-like particles across the blood–brain barrier

D. Ye, T. Zimmermann, V. Demina, S. Sotnikov, C. L. Ried, H. Rahn, M. Stapf, C. Untucht, M. Rohe, G. C. Terstappen, K. Wicke, M. Mezler, H. Manninga and A. H. Meyer, Nanoscale Adv., 2021, Advance Article , DOI: 10.1039/D0NA00879F

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