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Journal of Virology, April 2001, p. 3335-3342, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3335-3342.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Improved Adenovirus Vectors for Infection of Cardiovascular Tissues

M. J. E. Havenga,1,* A. A. C. Lemckert,1 J. M. Grimbergen,2 R. Vogels,1 L. G. M. Huisman,2 D. Valerio,1 A. Bout,1 and P. H. A. Quax2

Crucell Holland B.V., 2301 CA Leiden,1 and Gaubius Laboratory TNO-PG, 2301 CE Leiden,2 The Netherlands

Received 18 October 2000/Accepted 24 December 2000

To identify improved adenovirus vectors for cardiovascular gene therapy, a library of adenovirus vectors based on adenovirus serotype 5 (Ad5) but carrying fiber molecules of other human serotypes, was generated. This library was tested for efficiency of infection of human primary vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Based on luciferase, LacZ, or green fluorescent protein (GFP) marker gene expression, several fiber chimeric vectors were identified that displayed improved infection of these cell types. One of the viruses that performed particularly well is an Ad5 carrying the fiber of Ad16 (Ad5.Fib16), a subgroup B virus. This virus showed, on average, 8- and 64-fold-increased luciferase activities on umbilical vein ECs and SMCs, respectively, compared to the parent vector. GFP and lacZ markers showed that approximately 3-fold (ECs) and 10-fold (SMCs) more cells were transduced. Experiments performed with both cultured SMCs and organ cultures derived from different vascular origins (saphenous vein, iliac artery, left interior mammary artery, and aorta) and from different species demonstrated that Ad5.Fib16 consistently displays improved infection in primates (humans and rhesus monkeys). SMCs of the same vessels of rodents and pigs were less infectable with Ad5.Fib16 than with Ad5. This suggests that either the receptor for human Ad16 is not conserved between different species or that differences in the expression levels of the putative receptor exist. In conclusion, our results show that an Ad5-based virus carrying the fiber of Ad16 is a potent vector for the transduction of primate cardiovascular cells and tissues.

* Corresponding author. Mailing address: Crucell B.V., P.O. Box 2048, 2301 CA Leiden, The Netherlands. Phone: 3171-5248726. Fax: 3171-5248702. E-mail: m.havenga{at}crucell.com.

Journal of Virology, April 2001, p. 3335-3342, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3335-3342.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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