Terminal galactose residues on cell-surface glycans (Terminal galactose)

Terminal galactose residues are carbohydrate moieties located at the distal ends of N-linked glycans on the surface of various mammalian cells. These residues function as the primary attachment factor for Adeno-associated virus serotype 9 (AAV9), facilitating the initial docking of the viral capsid to the host cell membrane (Bell et al., 2011, J. Virol.). This interaction is highly specific to the AAV9 serotype and is mediated by a binding pocket formed by the capsid proteins VP1, VP2, and VP3. While the universal AAV receptor (AAVR) is required for subsequent endocytosis, terminal galactose is essential for the unique tissue tropism of AAV9, including its ability to cross the blood-brain barrier (Shen et al., 2011, J. Biol. Chem.). In therapeutic applications, this target is utilized by gene therapy agents such as onasemnogene abeparvovec (Zolgensma) to treat spinal muscular atrophy by ensuring efficient delivery to motor neurons and other systemic tissues. However, the widespread expression of galactose can lead to significant liver sequestration, presenting a challenge for targeted delivery and safety (Boutin et al., 2010, Gene Ther.).

Other names

Terminal β-D-galactoseN-linked terminal galactoseAAV9 attachment factorGalactose receptor

Acts as the primary attachment factor for the AAV9 capsid, facilitating viral binding to the cell surface prior to internalization via the universal AAV receptor (AAVR).