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J. Virol. doi:10.1128/JVI.00663-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo: A fundamental involvement of coagulation factors and redundancy of CAR binding by Ad5

Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF; British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK; Crucell, PO Bx 2048, 2301 CA Leiden, The Netherlands; Haemostasis and Thrombosis, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK

^* To whom correspondence should be addressed. Email: ab11f{at}clinmed.gla.ac.uk.

	Abstract

Vitamin K-dependent coagulation factors can promote adenoviral cell transduction in vitro. In vivo, warfarin pre-treatment ablates liver targeting of an Ad serotype 5 vector deleted in CAR binding capability. Here, we assess in vivo transduction and biodistribution of Ad5 vectors with non-modified fibers (Ad5) and a serotype 47 fiber pseudotyped Ad5 (Ad5/47; subgroup D) virus following intravascular injection. Warfarin reduced liver transduction by both viruses. However, no impact on early liver virus accumulation was observed suggesting no effect on Kupffer cell interactions. Hence, coagulation factors play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5 and Ad5/47 vectors.

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