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Journal of Virology, October 2000, p. 9540-9545, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A TVA-Single-Chain Antibody Fusion Protein Mediates Specific Targeting of a Subgroup A Avian Leukosis Virus Vector to Cells Expressing a Tumor-Specific Form of Epidermal Growth Factor Receptor

Sophie Snitkovsky,1,2 Thomas M. J. Niederman,3 Bob S. Carter,4 Richard C. Mulligan,3 and John A. T. Young2,5,*

Committee on Virology,1 Department of Microbiology and Molecular Genetics,2 Howard Hughes Medical Institute at the Children's Hospital,3 and Harvard Institute of Human Genetics,4 Harvard Medical School, Boston, Massachusetts 02115, and Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin at Madison, Madison, Wisconsin 537065

Received 12 April 2000/Accepted 28 July 2000

We have previously described an approach that employs retroviral receptor-ligand bridge proteins to target retroviral vectors to specific cell types. To determine whether targeted retroviral entry can also be achieved using a retroviral receptor-single-chain antibody bridge protein, the TVA-MR1 fusion protein was generated. TVA-MR1 is comprised of the extracellular domain of the TVA receptor for subgroup A avian leukosis viruses (ALV-A), fused to the MR1 single-chain antibody that binds specifically to EGFRvIII, a tumor-specific form of the epidermal growth factor receptor. We show that TVA-MR1 binds specifically to a murine version of EGFRvIII and promotes ALV-A entry selectively into cells that express this cell surface marker. These studies demonstrate that it is possible to target retroviral vectors to specific cell types through the use of a retroviral receptor-single-chain antibody fusion protein.


* Corresponding author. Mailing address: McArdle Laboratory for Cancer Research, University of Wisconsin at Madison, 1400 University Ave., Madison, WI 53706. Phone: (608) 265-5151. Fax: (608) 262-2824. E-mail: young{at}oncology.wisc.edu.


Journal of Virology, October 2000, p. 9540-9545, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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