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Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins
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SYSNO ASEP 0358495 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins Author(s) Bachtarzi, H. (GB)
Stevenson, M. (GB)
Šubr, Vladimír (UMCH-V) RID, ORCID
Ulbrich, Karel (UMCH-V) RID
Seymour, L. W. (GB)
Fisher, K. D. (GB)Source Title Journal of Controlled Release. - : Elsevier - ISSN 0168-3659
Roč. 150, č. 2 (2011), s. 196-203Number of pages 8 s. Language eng - English Country NL - Netherlands Keywords E-selectin ; pHPMA ; adenovirus Subject RIV EI - Biotechnology ; Bionics R&D Projects 1M0505 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) CEZ AV0Z40500505 - UMCH-V (2005-2011) UT WOS 000289701200010 DOI 10.1016/j.jconrel.2010.10.011 Annotation Adenovirus (Adluc) was coated with a reactive polymer based on poly[N-(2-hydroxypropyl)methacrylamide] to ablate normal infection pathways. Linkage of a monoclonal antibody against E-selectin demonstrated E-selectin-specific transduction of tumour necrosis factor-α (TNF-α)-activated endothelial cells. A two-component targeting system using protein G was developed. We report an enhancement in transduction of TNF-α-activated endothelium in vitro and ex vivo in a human umbilical vein cord model using the E-selectin antibody. Virus retargeted using a chimeric P-selectin Glycoprotein Ligand-1-Fc fusion (PSGL-1) protein showed better circulation kinetics and uptake into HepG2 xenografts following systemic administration in mice, with 36-fold higher genome copies, compared with non-modified virus. Immunohistochemistry of tumour sections from mice treated with PSGL-1-retargeted virus showed a co-localisation of luciferase with CD31 suggesting selective endothelial targeting. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2012
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