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Journal of Virology, November 2003, p. 11367-11377, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11367-11377.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Genetically Targeted Adenovirus Vector Directed to CD40-Expressing Cells

Natalya Belousova,¹ Nikolay Korokhov,² Valentina Krendelshchikova,¹ Vera Simonenko,¹ Galina Mikheeva,² Pierre L. Triozzi,³ Wayne A. Aldrich,³ Papia T. Banerjee,⁴ Stephen D. Gillies,⁴ David T. Curiel,¹ and Victor Krasnykh^1*

Division of Human Gene Therapy, Departments of Medicine, Pathology, and Surgery, and Gene Therapy Center,¹ Division of Hematology-Oncology, University of Alabama at Birmingham,³ VectorLogics, Inc., Birmingham, Alabama 35294,² EMD Lexigen Research Center, Billerica, Massachusetts 01821⁴

Received 20 May 2003/ Accepted 30 July 2003

The success of gene therapy depends on the specificity of transgene delivery by therapeutic vectors. The present study describes the use of an adenovirus (Ad) fiber replacement strategy for genetic targeting of the virus to human CD40, which is expressed by a variety of diseased tissues. The tropism of the virus was modified by the incorporation into its capsid of a protein chimera comprising structural domains of three different proteins: the Ad serotype 5 fiber, phage T4 fibritin, and the human CD40 ligand (CD40L). The tumor necrosis factor-like domain of CD40L retains its functional tertiary structure upon incorporation into this chimera and allows the virus to use CD40 as a surrogate receptor for cell entry. The ability of the modified Ad vector to infect CD40-positive dendritic cells and tumor cells with a high efficiency makes this virus a prototype of choice for the derivation of therapeutic vectors for the genetic immunization and targeted destruction of tumors.

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* Corresponding author. Present address: 1515 Holcombe Blvd., Unit 57, Houston, TX 77030. Phone: (713) 563-4873. Fax: (713) 563-4894. E-mail: vkrasnykh{at}di.mdacc.tmc.edu.

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Journal of Virology, November 2003, p. 11367-11377, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11367-11377.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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