Heparan Sulfate Proteoglycan Binding Properties of Adeno-Associated Virus Retargeting Mutants and Consequences for Their In Vivo Tropism-Reference-Cited by-同舟云学术

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

Published:2006-07-15 Issue:14 Volume:80 Page:7265-7269
ISSN:0022-538X
Container-title:Journal of Virology
language:en
Short-container-title:J Virol

Author:

Perabo Luca¹²,Goldnau Daniela¹²,White Kathryn³,Endell Jan¹²,Boucas Jorge²,Humme Sibille²⁴,Work Lorraine M.³,Janicki Hanna²,Hallek Michael¹²⁴⁵,Baker Andrew H.³,Büning Hildegard¹²⁴

Affiliation:

1. Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, Munich, Germany

2. Klinik I für Innere Medizin, Universität zu Köln,Joseph-Stelzmann-Str. 9, Cologne, Germany

3. British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, United Kingdom

4. Center for Molecular Medicine, Universität zu Köln, Joseph-Stelzmann-Str. 52, Cologne, Germany

5. Gesellschaft für Strahlenforschung-National Center for Research and Environment, Marchioninistr. 25, Munich, Germany

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/JVI.00076-06

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5. Identification of a Heparin-Binding Motif on Adeno-Associated Virus Type 2 Capsids

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