E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-.alpha.-activated human umbilical vein endothelial cells

0362894 - ÚMCH 2012 RIV GB eng J - Journal Article
Bachtarzi, H. - Stevenson, M. - Šubr, Vladimír - Seymour, L. W. - Fisher, K. D.
E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-.alpha.-activated human umbilical vein endothelial cells.
Journal of Drug Targeting. Roč. 19, č. 8 (2011), s. 690-700. ISSN 1061-186X. E-ISSN 1029-2330
Institutional research plan: CEZ:AV0Z40500505
Keywords : polymer-coated virus * vascular targeting * inflammation
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 2.696, year: 2011

Retargeting of adenovirus via E-selectin as a viable pathway of infection in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs) was investigated. E1, E3-deleted Ad5 expressing cytomegalovirus immediate-early promoter-driven luciferase (Adluc) was coated with a reactive multivalent copolymer based on poly [N-(2-hydroxypropyl) methacrylamide] to generate pHPMA-adenovirus (pcAdluc). This was then retargeted by covalent attachment of a mouse antihuman E-selectin monoclonal antibody (MHES mAb). MHESpcAdluc was efficiently taken up into HUVECs, generating a high level of transduction in TNF-α-treated E-selectin positive cells but not in untreated receptor-negative cells. Our results suggest that E-selectin could be a valuable target for gene transfer strategies internalizing polymer-coated adenovirus particles through a viable receptor-mediated endocytosis pathway, generating adequate levels of transgene expression per virus genome copy.
Permanent Link: http://hdl.handle.net/11104/0199069