JVI Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ried, M. U.
Right arrow Articles by Hallek, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ried, M. U.
Right arrow Articles by Hallek, M.

 Previous Article  |  Next Article 

Journal of Virology, May 2002, p. 4559-4566, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4559-4566.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Adeno-Associated Virus Capsids Displaying Immunoglobulin-Binding Domains Permit Antibody-Mediated Vector Retargeting to Specific Cell Surface Receptors

Martin U. Ried,1 Anne Girod,1 Kristin Leike,1 Hildegard Büning,1 and Michael Hallek1,2,3*

Laboratorium für Molekulare Biologie, Genzentrum,1 Medizinische Klinik III, Klinikum Grosshadern, Ludwig-Maximilians-Universitaet Muenchen,2 GSF-National Center for Research and Environment, KKG Gentherapie, 81377 Munich, Germany3

Received 10 September 2001/ Accepted 18 January 2002

Recombinant adeno-associated virus type 2 (rAAV2) is a promising vector for human somatic gene therapy. However, its broad host range is a disadvantage for some applications, because it reduces the specificity of the gene transfer. To overcome this limitation, we sought to create a versatile rAAV vector targeting system which would allow us to redirect rAAV binding to specific cell surface receptors by simple coupling of different ligands to its capsid. For this purpose, an immunoglobulin G (IgG) binding domain of protein A, Z34C, was inserted into the AAV2 capsid at amino acid position 587. The resulting AAV2-Z34C mutants could be packaged and purified to high titers and bound to IgG molecules. rAAV2-Z34C vectors coupled to antibodies against CD29 (ß1-integrin), CD117 (c-kit receptor), and CXCR4 specifically transduced distinct human hematopoietic cell lines. In marked contrast, no transduction was seen in the absence of antibodies or in the presence of specific blocking reagents. These results demonstrate for the first time that an immunoglobulin binding domain can be inserted into the AAV2 capsid and coupled to various antibodies, which mediate the retargeting of rAAV vectors to specific cell surface receptors.

* Corresponding author. Mailing address: Genzentrum, Universitaet Muenchen, Feodor-Lynen-Str. 25, D-81377 Munich, Germany. Phone: 49-89-2180-6774. Fax: 49-89-2180-6797. E-mail: mhallek{at}med3.med.uni-muenchen.de.

Journal of Virology, May 2002, p. 4559-4566, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4559-4566.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Mol. Cell. Biol. Microbiol. Mol. Biol. Rev.
Clin. Vaccine Immunol. ALL ASM JOURNALS

Copyright © 2002 by the American Society for Microbiology. All rights reserved.