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Journal of Virology, May 2002, p. 4612-4620, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4612-4620.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Exploiting the Natural Diversity in Adenovirus Tropism for Therapy and Prevention of Disease

M. J. E. Havenga,1* A. A. C. Lemckert,1 O. J. A. E. Ophorst,1 M. van Meijer,1 W. T. V. Germeraad,1 J. Grimbergen,2 M. A. van den Doel,3 R. Vogels,1 J. van Deutekom,4 A. A. M. Janson,4 J. D. de Bruijn,3 F. Uytdehaag,1 P. H. A. Quax,2 T. Logtenberg,1 M. Mehtali,1 and A. Bout1

Crucell Holland B.V., 2301 CA Leiden,1 TNO-PG Gaubius Laboratory, 2301 CE Leiden,2 Department of Human and Clinical Genetics, Leiden University Medical Center, 2300 RA Leiden,4 IsoTis NV, 3720 MB Bilthoven, The Netherlands3

Received 2 October 2001/ Accepted 30 January 2002

Since targeting of recombinant adenovirus vectors to defined cell types in vivo is a major challenge in gene therapy and vaccinology, we explored the natural diversity in human adenovirus tissue tropism. Hereto, we constructed a library of Ad5 vectors carrying fibers from other human serotypes. From this library, we identified vectors that efficiently infect human cells that are important for diverse gene therapy approaches and for induction of immunity. For several medical applications (prenatal diagnosis, artificial bone, vaccination, and cardiovascular disease), we demonstrate the applicability of these novel vectors. In addition, screening cell types derived from different species revealed that cellular receptors for human subgroup B adenoviruses are not conserved between rodents and primates. These results provide a rationale for utilizing elements of human adenovirus serotypes to generate chimeric vectors that improve our knowledge concerning adenovirus biology and widen the therapeutic window for vaccination and many different gene transfer applications.

* Corresponding author. Mailing address: Crucell Holland B.V., P.O. Box 2048, 2301 CA Leiden, The Netherlands. Phone: 31 (0) 71 5248736. Fax: 31 (0) 71 5248702. E-mail: m.havenga{at}crucell.com.

Journal of Virology, May 2002, p. 4612-4620, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4612-4620.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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