Terminal galactose residues on N-linked glycans (Terminal Gal)

Terminal galactose residues on cell-surface N-linked glycans, frequently referred to as "N-terminal galactose" in viral literature, serve as the primary attachment factors and receptors for Adeno-associated virus serotype 9 (AAV9). These residues are typically masked by terminal sialic acid in healthy tissues, and their exposure—often termed asialoglycan formation—is a critical determinant of viral tropism and the clearance of glycoproteins from circulation. AAV9-based gene therapies, such as onasemnogene abeparvovec, exploit these terminal galactose moieties to achieve widespread tissue transduction, including the ability to cross the blood-brain barrier. Beyond their role in viral entry, terminal galactose residues are recognized by endogenous lectins like galectins and the asialoglycoprotein receptor (ASGPR), which mediate processes such as cell signaling, immune response, and hepatic protein turnover. In pathological states like cancer, the increased exposure of terminal galactose (e.g., the T-antigen) is a well-known biomarker of malignancy and a potential target for therapeutic lectins or antibodies. Consequently, these glycans are pivotal in both the natural regulation of protein homeostasis and the development of advanced gene delivery systems.

Other names

N-terminal galactose residuesNon-reducing terminal galactoseTerminal galactoseAsialoglycansGalactose-terminated glycansTerminal beta-galactose

Binding of viral capsids (e.g., AAV9) to terminal galactose residues on cell-surface N-linked glycans to facilitate viral attachment, endocytosis, and subsequent cellular transduction.