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Science 19 November 1999:
Vol. 286. no. 5444, pp. 1568 - 1571
DOI: 10.1126/science.286.5444.1568
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Reports

Identification of a Conserved Receptor-Binding Site on the Fiber Proteins of CAR-Recognizing Adenoviridae

Peter W. Roelvink, * Gai Mi Lee, David A. Einfeld, Imre Kovesdi, Thomas J. Wickham

The human adenovirus serotype 5 (Ad5) is used widely for applications in human gene therapy. Cellular attachment of Ad5 is mediated by binding of the carboxyl-terminal knob of its fiber coat protein to the Coxsackie adenovirus receptor (CAR) protein. However, Ad5 binding to CAR hampers the development of adenovirus vectors capable of specifically targeting (diseased) tissues or organs. Through sequence analysis and mutagenesis, a conserved receptor-binding region was identified on the side of three divergent CAR-binding knobs. The feasibility of simultaneous CAR ablation and redirection of an adenovirus to a new receptor is demonstrated.

Research and Development, GenVec Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20879, USA.
*   To whom correspondence should be addressed. E-mail: genecloner{at}genvec.com

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