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Journal of Virology, September 2007, p. 9568-9571, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00663-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Targeting of Adenovirus Serotype 5 (Ad5) and 5/47 Pseudotyped Vectors In Vivo: Fundamental Involvement of Coagulation Factors and Redundancy of CAR Binding by Ad5{triangledown}

Simon N. Waddington,1 Alan L. Parker,2 Menzo Havenga,3 Stuart A. Nicklin,2 Suzanne M. K. Buckley,1 John H. McVey,4 and Andrew H. Baker2*

Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF, United Kingdom,1 British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom,2 Crucell, P.O. Box 2048, 2301 CA Leiden, The Netherlands,3 Haemostasis and Thrombosis, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom4

Received 28 March 2007/ Accepted 29 May 2007

Vitamin K-dependent coagulation factors can promote adenoviral cell transduction in vitro. In vivo, warfarin pretreatment ablates liver targeting of an adenovirus serotype 5 (Ad5) vector deleted of CAR binding capability. Here, we assess in vivo transduction and biodistribution of Ad5 vectors with nonmodified 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.

* Corresponding author. Mailing address: Division of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom. Phone: 44 141 330 1977. Fax: 44 141 330 6997. E-mail: ab11f{at}clinmed.gla.ac.uk

{triangledown} Published ahead of print on 6 June 2007.

Journal of Virology, September 2007, p. 9568-9571, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00663-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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