Binding of Adeno-associated Virus Type 5 to 2,3-Linked Sialic Acid Is Required for Gene Transfer

Recombinant adeno-associated viruses (AAV) are promising gene therapy vectors. Whereas AAV serotype 2-mediated gene transfer to muscle has partially replaced factor IX deficiency in hemophilia patients, its ability to mediate gene transfer to the lungs for cystic fibrosis is hindered by lack of apic...

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Published in:The Journal of biological chemistry 2001-06, Vol.276 (23), p.20610-20616
Main Authors: Walters, Robert W., Yi, Su Min P., Keshavjee, Shaf, Brown, Kevin E., Welsh, Michael J., Chiorini, John A., Zabner, Joseph
Format: Article
Language:English
Subjects:
Adeno-associated virus 5
Animals
Cell Line
Dependovirus - genetics
Dependovirus - metabolism
Gene Transfer Techniques
Genetic Vectors
Hemagglutination Tests
Humans
Membrane Fusion
N-Acetylneuraminic Acid - metabolism
sialic acid
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Summary:Recombinant adeno-associated viruses (AAV) are promising gene therapy vectors. Whereas AAV serotype 2-mediated gene transfer to muscle has partially replaced factor IX deficiency in hemophilia patients, its ability to mediate gene transfer to the lungs for cystic fibrosis is hindered by lack of apical receptors. However, AAV serotype 5 infects human airway epithelia from the lumenal surface. We found that in contrast to AAV2, the apical membrane of airway epithelia contains abundant high affinity receptors for AAV5. Binding and gene transfer with AAV5 was abolished by genetic or enzymatic removal of sialic acid from the cell surface. Furthermore, binding and gene transfer to airway epithelia was competed by lectins that specifically bind 2,3-linked sialic acid. These observations suggest that 2,3-linked sialic acid is either a receptor for AAV5 or it is a necessary component of a receptor complex. Further elucidation of the receptor for this virus should enhance understanding of parvovirus biology and expand the therapeutic targets for AAV vectors.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M101559200