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Journal of Virology, December 1998, p. 10148-10156, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cell-Type-Specific Gene Transfer into Human Cells with Retroviral Vectors That Display Single-Chain Antibodies

An Jiang,1 Te-Hua T. Chu,1,dagger F. Nocken,2 Klaus Cichutek,2 and Ralph Dornburg1,*

Division of Infectious Diseases, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,1 and Paul Ehrlich Institut, 63225 Langen, Germany2

Received 20 April 1998/Accepted 10 September 1998

The successful application of human gene therapy protocols on a broad clinical basis will depend on the availability of in vivo cell-type-specific gene delivery systems. We have developed retroviral vector particles, derived from spleen necrosis virus (SNV), that display the antigen binding site of an antibody on the viral surface. Using retroviral vectors derived from SNV that displayed single-chain antibodies (scAs) directed against a carcinoembryonic antigen-cross-reacting cell surface protein, we have shown that an efficient, cell-type-specific gene delivery can be obtained. In this study, we tested whether other scAs displayed on SNV vector particles can also lead to cell-type-specific gene delivery. We displayed the following scAs on the retroviral surface: one directed against the human cell surface antigen Her2neu, which belongs to the epidermal growth factor receptor family; one directed against the stem cell-specific antigen CD34; and one directed against the transferrin receptor, which is expressed on liver cells and various other tissues. We show that retroviral vectors displaying these scAs are competent for infection in human cells which express the antigen recognized by the scA. Infectivity was cell type specific, and titers above 105 CFU per ml of tissue culture supernatant medium were obtained. The density of the antigen on the target cell surface does not influence virus titers in vitro. Our data indicate that the SNV vector system is well suited for the development of a large variety of cell-type-specific targeting vectors.

* Corresponding author. Mailing address: Division of Infectious Diseases, Thomas Jefferson University, Jefferson Alumni Hall, 1020 Locust St., Suite 329, Philadelphia, PA 19107. Phone: (215) 503-3117. Fax: (215) 923-1956. E-mail: rpomvicl{at}jeflin.tju.edu.

dagger Present address: New York Blood Center, Department of Immunochemistry, New York, NY 10021.

Journal of Virology, December 1998, p. 10148-10156, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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