Vectors based on adeno-associated virus (AAV) serotype 9 are candidates for in vivo gene delivery to many organs, but the receptor(s) mediating these tropisms have yet to be defined. We evaluated AAV9 uptake by glycans with terminal sialic acids (SAs), a common mode of cellular entry for viruses. We found, however, that AAV9 binding increased when terminal SA was enzymatically removed, suggesting that galactose, which is the most commonly observed penultimate monosaccharide to SA, may mediate AAV9 transduction. This was confirmed in mutant CHO Pro-5 cells deficient in the enzymes involved in glycoprotein biogenesis, as well as lectin interference studies. Binding of AAV9 to glycans with terminal galactose was demonstrated via glycan binding assays. Co-instillation of AAV9 vector with neuraminidase into mouse lung resulted in exposure of terminal galactose on the apical surface of conducting airway epithelial cells, as shown by lectin binding and increased transduction of these cells, demonstrating the possible utility of this vector in lung-directed gene transfer. Increasing the abundance of the receptor on target cells and improving vector efficacy may improve delivery of AAV vectors to their therapeutic targets.
Christie L. Bell, Luk H. Vandenberghe, Peter Bell, Maria P. Limberis, Guang-Ping Gao, Kim Van Vliet, Mavis Agbandje-McKenna, James M. Wilson
Title and authors | Publication | Year |
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G McGillivary, ZB Jordan, ME Peeples, LO Bakaletz |
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Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza
MP Limberis, VS Adam, G Wong, J Gren, D Kobasa, TM Ross, GP Kobinger, A Tretiakova, JM Wilson |
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S Park, JC Gildersleeve, O Blixt, I Shin |
Chemical Society Reviews | 2013 |
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B Venkatakrishnan, J Yarbrough, J Domsic, A Bennett, B Bothner, OG Kozyreva, RJ Samulski, N Muzyczka, R McKenna, M Agbandje-McKenna |
Journal of virology | 2013 |
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MJ Castle, E Perlson, EL Holzbaur, JH Wolfe |
Molecular Therapy | 2013 |
Efficient gene delivery and selective transduction of astrocytes in the mammalian brain using viral vectors
N Merienne, JL Douce, E Faivre, N Déglon, G Bonvento |
2013 | |
Engraftment of a Galactose Receptor Footprint onto Adeno-associated Viral Capsids Improves Transduction Efficiency
S Shen, ED Horowitz, AN Troupes, SM Brown, N Pulicherla, RJ Samulski, M Agbandje-McKenna, A Asokan |
2013 | |
Differential Adeno-Associated Virus Serotype-Specific Interaction Patterns with Synthetic Heparins and Other Glycans
M Mietzsch, F Broecker, A Reinhardt, PH Seeberger, R Heilbronn, MJ Imperiale |
Journal of virology | 2013 |
Comparative Analysis of Adeno-Associated Virus Capsid Stability and Dynamics
V Rayaprolu, S Kruse, R Kant, B Venkatakrishnan, N Movahed, D Brooke, B Lins, A Bennett, T Potter, R McKenna, M Agbandje-McKenna, B Bothner |
Journal of virology | 2013 |
Multiple Roles for Sialylated Glycans in Determining the Cardiopulmonary Tropism of Adeno-Associated Virus 4
S Shen, AN Troupes, N Pulicherla, A Asokan |
Journal of virology | 2013 |