Year: 2011
Type: article
Abstract: 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.
DOI: 10.1172/jci57367
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: Gene therapy training: CF and genetic diseases, Gene Therapy for Lung and Cardiovascular Disease, G3549828030, Molecular Therapy for Cystic Fibrosis, G5520316217, AAV Gene Therapy for Lipid Disorders, Protein Carbohydrate Interactions in Cell Communication, AAV capsids and their cellular interactions
OpenAlex ID: W2166540858