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Journal of Virology, October 1999, p. 8689-8695, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Chimeric Type 2 Adenovirus Vector with a Type 17 Fiber Enhances Gene Transfer to Human Airway Epithelia

Joseph Zabner,1,* Miguel Chillon,1 Teresa Grunst,1 Thomas O. Moninger,1 Beverly L. Davidson,1 Richard Gregory,2 and Donna Armentano2

Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242,1 and Department of Gene Therapy, Genzyme Corp., Framingham Massachusetts 017092

Received 16 December 1998/Accepted 21 June 1999

In studies of the genetic disease cystic fibrosis, recombinant adenovirus type 2 (Ad2) and Ad5 are being investigated as vectors to transfer cystic fibrosis transmembrane conductance regulator cDNA to airway epithelia. However, earlier work has shown that human airway epithelia are resistant to infection by Ad2 and Ad5. Therefore, we examined the efficiency of other adenovirus serotypes at infecting airway epithelia. We found that several serotypes of adenoviruses, in particular, wild-type Ad17, infected a greater number of cells than wild-type Ad2. The increased efficiency of wild-type Ad17 could be explained by increased fiber-dependent binding to the epithelia. Therefore, we constructed a chimeric virus, Ad2(17f)/beta Gal-2, which is identical to Ad2/beta Gal-2 with the exception of having the fiber protein of Ad17 replace Ad2 fiber. This vector retained the increased binding and efficiency of gene transfer to well-differentiated human airway epithelia. These data suggest that inclusion of Ad17 fiber into adenovirus vectors may improve the outlook for gene delivery to human airway epithelia.

* Corresponding author. Mailing address: University of Iowa College of Medicine, 500 EMRB, Iowa City, IA 52242. Phone: (319) 353-5511. Fax: (319) 353-5572. E-mail: Joseph-Zabner{at}uiowa.edu.

Journal of Virology, October 1999, p. 8689-8695, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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