Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers

Abstract

Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type, and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than in monolayers. Through experiments involving assessing enzyme degradation of cell surface proteoglycans, this change could not be attributed to differences in the extra cellular matrix (ECM), but a similar change in AAV 5 transduction efficiency could be readily explained by differences in cell surface sialylated glycan. Unexpectedly it was found that in a small but diverse sample of horses evidence for serum neutralizing antibodies was only found to AAV 5. This suggests a unique relationship between this capsid and the equine host or an unresolved relationship between similar bovine AAV and the AAV 5 capsid immune response.