Terminal N-linked galactose (Gal)

Terminal N-linked galactose residues are the primary cell-surface receptors recognized by adeno-associated virus serotype 9 (AAV9) (Bell et al., 2011). These glycans are typically exposed when terminal sialic acids are removed or are absent, and they play a critical role in the attachment and internalization of AAV9 into host cells (Shen et al., 2011). This interaction is a key determinant of the broad tissue tropism of AAV9, including its unique ability to cross the blood-brain barrier and transduce neurons and astrocytes (Pattali et al., 2019). In the context of gene therapy, these glycans are the target for AAV9-based delivery systems, such as the FDA-approved drug Zolgensma (onasemnogene abeparvovec) for spinal muscular atrophy (Novartis, 2020). Understanding and modulating the binding affinity to these glycans is essential for optimizing vector distribution and minimizing off-target effects like liver sequestration (Shen et al., 2012).

Other names

Terminal galactoseTerminal beta-galactoseAsialo N-glycansN-linked glycans with terminal galactoseBeta-1,4-galactose

The AAV9 capsid binds to terminal N-linked galactose residues on the cell surface, which serves as the primary attachment factor for viral entry and determines the vector's unique tissue tropism (Bell et al., 2011; Shen et al., 2011).