Terminal galactose-containing N-linked glycan (Gal-glycan)

Terminal galactose-containing N-linked glycans serve as the primary attachment receptors for the adeno-associated virus serotype 9 (AAV9) capsid on the host cell surface (Bell et al., 2011). Unlike many other AAV serotypes that utilize heparan sulfate proteoglycans, AAV9 specifically recognizes and binds to these terminal galactose residues to initiate infection (Shen et al., 2011). This interaction is a critical determinant of AAV9's unique tissue tropism, including its notable ability to cross the blood-brain barrier and transduce neurons and cardiomyocytes (Mendell et al., 2017). In the context of gene therapy, this receptor-ligand interaction is exploited to deliver therapeutic transgenes for treating various genetic disorders, most notably spinal muscular atrophy via the drug onasemnogene abeparvovec. The binding occurs at a specific pocket on the AAV9 capsid surface, which recognizes the galactose moiety with high affinity (Huang et al., 2016). However, the widespread expression of these glycans also leads to significant vector sequestration in the liver, which can result in dose-limiting hepatotoxicity and other systemic safety concerns (Duan, 2018).

Other names

Terminal galactoseN-linked galactoseAAV9 receptorGalactose-containing N-glycan

The AAV9 capsid binds specifically to terminal galactose residues on N-linked glycans, facilitating viral attachment to the host cell surface and subsequent internalization via receptor-mediated endocytosis.