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

Autor:	Ye D; AbbVie Deutschland GmbH & Co. KG, DMPK, Bioanalytical Research Knollstraße 67061 Ludwigshafen Germany dong.ye@abbvie.com axel.meyer@abbvie.com., Zimmermann T; AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery Knollstraße 67061 Ludwigshafen Germany., Demina V; NEUWAY Pharma GmbH Ludwig-Erhard-Allee 2 53175 Bonn Germany., Sotnikov S; NEUWAY Pharma GmbH Ludwig-Erhard-Allee 2 53175 Bonn Germany., Ried CL; AbbVie Deutschland GmbH & Co. KG, Development Sciences NBE Knollstraße 67061 Ludwigshafen Germany., Rahn H; AbbVie Deutschland GmbH & Co. KG, Development Sciences NBE Knollstraße 67061 Ludwigshafen Germany., Stapf M; NEUWAY Pharma GmbH Ludwig-Erhard-Allee 2 53175 Bonn Germany., Untucht C; AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery Knollstraße 67061 Ludwigshafen Germany., Rohe M; AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery Knollstraße 67061 Ludwigshafen Germany., Terstappen GC; AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery Knollstraße 67061 Ludwigshafen Germany., Wicke K; AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery Knollstraße 67061 Ludwigshafen Germany., Mezler M; AbbVie Deutschland GmbH & Co. KG, DMPK, Bioanalytical Research Knollstraße 67061 Ludwigshafen Germany dong.ye@abbvie.com axel.meyer@abbvie.com., Manninga H; NEUWAY Pharma GmbH Ludwig-Erhard-Allee 2 53175 Bonn Germany., Meyer AH; AbbVie Deutschland GmbH & Co. KG, DMPK, Bioanalytical Research Knollstraße 67061 Ludwigshafen Germany dong.ye@abbvie.com axel.meyer@abbvie.com.
Jazyk:	angličtina
Zdroj:	Nanoscale advances [Nanoscale Adv] 2021 Feb 09; Vol. 3 (9), pp. 2488-2500. Date of Electronic Publication: 2021 Feb 09 (Print Publication: 2021).
DOI:	10.1039/d0na00879f
Abstrakt:	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. Competing Interests: Dong Ye, Christian L. Ried, Harri Rahn, Christopher Untucht, Karsten Wicke, Mario Mezler and Axel H. Meyer are employees of AbbVie and may own AbbVie stock. Victoria Demina, Sergey Sotnikov, Marcus Stapf and Heiko Manninga are employees of NEUWAY Pharma GmbH. Tina Zimmermann, Georg C. Terstappen and Michael Rohe were employees of AbbVie at the time when they contributed to this work. Currently, Tina Zimmermann is an employee of Boehringer Ingelheim Pharma; Georg C. Terstappen is an employee of Cambrian Biopharma; Michael Rohe is an employee of H. Lundbeck A/S. All authors declare no competing financial interest in this work. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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