Identification of the galactose binding domain of the adeno-associated virus serotype 9 capsid.

Abstract:

:Adeno-associated virus serotype 9 (AAV9) vectors show promise for gene therapy of a variety of diseases due to their ability to transduce multiple tissues, including heart, skeletal muscle, and the alveolar epithelium of the lung. In addition, AAV9 is unique compared to other AAV serotypes in that it is capable of surpassing the blood-brain barrier and transducing neurons in the brain and spinal cord. It has recently been shown that AAV9 uses galactose as a receptor to transduce many different cell types in vitro, as well as cells of the mouse airway in vivo. In this study, we sought to identify the specific amino acids of the AAV9 capsid necessary for binding to galactose. By site-directed mutagenesis and cell binding assays, plus computational ligand docking studies, we discovered five amino acids, including N470, D271, N272, Y446, and W503, which are required for galactose binding that form a pocket at the base of the protrusions around the icosahedral 3-fold axes of symmetry. The importance of these amino acids for tissue tropism was also confirmed by in vivo studies in the mouse lung. Identifying the interactions necessary for AAV9 binding to galactose may lead to advances in vector engineering.

journal_name

J Virol

journal_title

Journal of virology

authors

Bell CL,Gurda BL,Van Vliet K,Agbandje-McKenna M,Wilson JM

doi

10.1128/JVI.00448-12

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

7326-33

issue

13

eissn

0022-538X

issn

1098-5514

pii

JVI.00448-12

journal_volume

86

pub_type

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