This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Volpers, C. Articles by Lochmüller, H. Search for Related Content PubMed PubMed Citation Articles by Volpers, C. Articles by Lochmüller, H.

 Previous Article  |  Next Article 

Journal of Virology, February 2003, p. 2093-2104, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2093-2104.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antibody-Mediated Targeting of an Adenovirus Vector Modified To Contain a Synthetic Immunoglobulin G-Binding Domain in the Capsid

Center for Molecular Medicine (ZMMK) and Institute for Genetics, University of Cologne, D-50931 Cologne,¹ Gene Center, Friedrich Baur Institute,² Department of Neurology, University of Munich, D-81377 Munich,³ Cardion AG, D-40699 Erkrath,⁴ Nikolaus Fiebinger Center for Molecular Medicine, University of Erlangen, D-91054 Erlangen, Germany⁵

Received 20 June 2002/ Accepted 4 November 2002

Adenovirus vectors have been targeted to different cell types by genetic modification of the capsid or by using recombinant or chemically engineered adaptor molecules. However, both genetic capsid modifications and bridging adaptors have to be specifically tailored for each particular targeting situation. Here, we present an efficient and versatile strategy allowing the direct use of monoclonal antibodies against cell surface antigens for targeting of adenovirus vectors. A synthetic 33-amino-acid immunoglobulin G (IgG)-binding domain (Z33) derived from staphylococcal protein A was inserted into the adenovirus fiber protein. The fiber retained the ability to assemble into trimers, bound IgG with high affinity (K_d = 2.4 nM), and was incorporated into vector particles. The transduction efficiency of the Z33-modified adenovirus vector in epidermal growth factor receptor (EGFR)-expressing cells was strongly and dose-dependently enhanced by combination with an EGFR-specific monoclonal antibody. The antibody-mediated increase in cellular transduction was abolished in the presence of competing protein A. In targeting experiments with differentiated primary human muscle cells, up to a 77-fold increase in reporter gene transfer was achieved by preincubation of the vector with monoclonal antibodies directed against neuronal cell adhesion molecule or integrin ₇, respectively. The IgG-binding adenovirus vector holds promise for directed gene transfer to a wide variety of cell types by simply changing the target-specific antibody.

This article has been cited by other articles:

• Tanaka, T., Huang, J., Hirai, S., Kuroki, M., Kuroki, M., Watanabe, N., Tomihara, K., Kato, K., Hamada, H. (2006). Carcinoembryonic Antigen-Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors.. Clin. Cancer Res. 12: 3803-3813 [Abstract] [Full Text]  
• Korokhov, N., Mikheeva, G., Krendelshchikov, A., Belousova, N., Simonenko, V., Krendelshchikova, V., Pereboev, A., Kotov, A., Kotova, O., Triozzi, P. L., Aldrich, W. A., Douglas, J. T., Lo, K.-M., Banerjee, P. T., Gillies, S. D., Curiel, D. T., Krasnykh, V. (2003). Targeting of Adenovirus via Genetic Modification of the Viral Capsid Combined with a Protein Bridge. J. Virol. 77: 12931-12940 [Abstract] [Full Text]