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Journal of Virology, October 2003, p. 11094-11104, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11094-11104.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

General Strategy for Broadening Adenovirus Tropism

Laura Fontana, Maurizio Nuzzo, Lorena Urbanelli, and Paolo Monaci*

Department of Molecular & Cell Biology, I.R.B.M. P. Angeletti, Pomezia, Rome, Italy

Received 6 June 2003/ Accepted 18 July 2003

In spite of its broad host range, adenovirus type 5 (Ad5) transduces a number of clinically relevant tissues and cell types inefficiently, mostly because of low expression of the coxsackievirus-adenovirus receptor (CAR). To improve gene transfer to such cells, we modified the Ad5 fiber knob to recognize novel receptors. We expressed a functional Ad5 fiber knob domain on the capsid of phage {lambda} and employed this display system to construct a large collection of ligands in the HI loop of the Ad5 knob. Panning this library on the CAR-negative mouse fibroblast cell line NIH 3T3 resulted in the identification of three clones with increased binding to these cells. Adenoviruses incorporating these ligands in the fiber gene transduced NIH 3T3 cells 2 or 3 orders of magnitude better than the parent vector. The same nonnative tropism was revealed in other cell types, independently of CAR expression. These Ad5 derivatives proved capable of transducing mouse and human primary immature dendritic cells with up to 100-fold increased efficiency.

* Corresponding author. Mailing address: Molecular & Cell Biology Department, I.R.B.M. P. Angeletti, Via Pontina km 30.6, 00040, Pomezia, Rome, Italy. Phone: 39 06 91093 242. Fax: 39 06 91093 654. E-mail: paolo_monaci{at}merck.com.

Journal of Virology, October 2003, p. 11094-11104, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11094-11104.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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