Cell-surface terminal galactose residues on N-linked glycoconjugates (Terminal Gal)

Cell-surface terminal galactose residues on N-linked glycoconjugates are carbohydrate structures found at the non-reducing ends of complex glycans attached to proteins. These residues are typically capped by sialic acid in healthy tissues; however, their exposure (desialylation) serves as a critical biological signal for protein aging and clearance. They function as the primary cellular receptor for Adeno-associated virus serotype 9 (AAV9), making them essential for the delivery of gene therapies like onasemnogene abeparvovec. Additionally, terminal galactose is recognized by the asialoglycoprotein receptor (ASGPR) in the liver, which mediates the removal of desialylated glycoproteins from circulation. In diseases such as rheumatoid arthritis, a deficiency in terminal galactose on IgG (the G0 glycoform) is a well-known biomarker of inflammation and disease activity.

Other names

Terminal beta-galactoseAsialoglycanGalactose-terminated N-glycanAAV9 receptor glycanTerminal Gal

AAV9-based gene therapies utilize terminal galactose residues on N-linked glycoconjugates as a primary attachment factor to facilitate cell surface binding and subsequent internalization. In physiological contexts, these residues act as ligands for the asialoglycoprotein receptor (ASGPR), which triggers the endocytosis and lysosomal degradation of glycoproteins that have lost their terminal sialic acid caps.