Terminal N-linked galactose-containing glycans (Galactose)

Cell-surface glycan receptors for the adeno-associated virus serotype 9 (AAV9) capsid primarily consist of N-linked glycans with terminal galactose residues. Unlike many other AAV serotypes that utilize sialic acid or heparan sulfate for attachment, AAV9 specifically recognizes and binds to terminal β-galactose linkages to initiate cell attachment and subsequent internalization [4, 8, 9]. This glycan-mediated interaction is a critical determinant of AAV9's unique tissue tropism, which includes its notable ability to cross the blood-brain barrier and transduce neurons and astrocytes throughout the central nervous system [13, 17]. In clinical applications, this receptor serves as the primary gateway for AAV9-based gene therapies, such as onasemnogene abeparvovec, which is used to treat spinal muscular atrophy [13, 18]. However, the widespread distribution of these glycans, particularly in the liver, can lead to significant hepatic sequestration and associated toxicity at high therapeutic doses [5, 20]. Understanding the density and presentation of these terminal galactose residues is essential for optimizing vector delivery and minimizing off-target effects in gene therapy protocols [6, 11].

Other names

Terminal galactoseN-linked galactosyl residuesβ-D-galactoseAAV9 glycan receptorTerminal β-galactose linkages

Viral attachment and entry mediated by capsid binding to terminal galactose residues on cell surface glycans