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Journal of Virology, May 2001, p. 4176-4183, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4176-4183.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Genetic Targeting of an Adenovirus Vector via Replacement of the Fiber Protein with the Phage T4 Fibritin

Victor Krasnykh,1,2 Natalya Belousova,1 Nikolay Korokhov,2 Galina Mikheeva,2 and David T. Curiel1,*

Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham,1 and VectorLogics, Inc.,2 Birmingham, Alabama 35294

Received 27 October 2000/Accepted 2 February 2001

The utility of adenovirus (Ad) vectors for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural conflicts between the fiber and the targeting ligand. Here we present a strategy to derive an Ad vector with enhanced targeting potential by a radical replacement of the fiber protein in the Ad capsid with a chimeric molecule containing a heterologous trimerization motif and a receptor-binding ligand. Our approach, which capitalized upon the overall structural similarity between the human Ad type 5 (Ad5) fiber and bacteriophage T4 fibritin proteins, has resulted in the generation of a genetically modified Ad5 incorporating chimeric fiber-fibritin proteins targeted to artificial receptor molecules. Gene transfer studies employing this novel viral vector have demonstrated its capacity to efficiently deliver a transgene payload to the target cells in a receptor-specific manner.

* Corresponding author. Mailing address: 1824 Sixth Ave. South, WTI 620, Birmingham, AL 35294. Phone: (205) 934-8627. Fax: (205) 975-7476. E-mail: David.Curiel{at}ccc.uab.edu.

Journal of Virology, May 2001, p. 4176-4183, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4176-4183.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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