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 Perabo, L. Articles by Büning, H. Search for Related Content PubMed PubMed Citation Articles by Perabo, L. Articles by Büning, H.

 Previous Article  |  Next Article 

Journal of Virology, July 2006, p. 7265-7269, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00076-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Heparan Sulfate Proteoglycan Binding Properties of Adeno-Associated Virus Retargeting Mutants and Consequences for Their In Vivo Tropism

Luca Perabo,^1,2, Daniela Goldnau,^1,2, Kathryn White,^3, Jan Endell,^1,2, Jorge Boucas,² Sibille Humme,^2,4 Lorraine M. Work,³ Hanna Janicki,² Michael Hallek,^1,2,4,5 Andrew H. Baker,³ and Hildegard Büning^1,2,4*

Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, Munich, Germany,¹ Klinik I für Innere Medizin, Universität zu Köln,Joseph-Stelzmann-Str. 9, Cologne, Germany,² British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, United Kingdom,³ Center for Molecular Medicine, Universität zu Köln, Joseph-Stelzmann-Str. 52, Cologne, Germany,⁴ Gesellschaft für Strahlenforschung-National Center for Research and Environment, Marchioninistr. 25, Munich, Germany⁵

Received 11 January 2006/ Accepted 15 April 2006

Adeno-associated virus type 2 (AAV-2) targeting vectors have been generated by insertion of ligand peptides into the viral capsid at amino acid position 587. This procedure ablates binding of heparan sulfate proteoglycan (HSPG), AAV-2's primary receptor, in some but not all mutants. Using an AAV-2 display library, we investigated molecular mechanisms responsible for this phenotype, demonstrating that peptides containing a net negative charge are prone to confer an HSPG nonbinding phenotype. Interestingly, in vivo studies correlated the inability to bind to HSPG with liver and spleen detargeting in mice after systemic application, suggesting several strategies to improve efficiency of AAV-2 retargeting to alternative tissues.

These authors contributed equally to this work.

This article has been cited by other articles:

• Grimm, D., Lee, J. S., Wang, L., Desai, T., Akache, B., Storm, T. A., Kay, M. A. (2008). In Vitro and In Vivo Gene Therapy Vector Evolution via Multispecies Interbreeding and Retargeting of Adeno-Associated Viruses. J. Virol. 82: 5887-5911 [Abstract] [Full Text]