Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

Thomas F. Lerch, Michael S. Chapman

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

Original languageEnglish (US)
Pages (from-to)6-13
Number of pages8
JournalVirology
Volume423
Issue number1
DOIs
StatePublished - Feb 5 2012

Keywords

  • Adeno-associated virus
  • Heparan sulfate
  • Heparin
  • Receptor

ASJC Scopus subject areas

  • Virology

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