Terminal galactose-containing glycans and Adeno-associated virus receptor (AAVR) (Gal/AAVR)

Hepatocyte surface glycans, specifically those featuring terminal galactose residues, serve as the primary attachment factors for Adeno-associated virus serotype 9 (AAV9) in the liver (Bell et al., 2011). Following initial glycan binding, the virus utilizes the Adeno-associated virus receptor (AAVR), a transmembrane protein encoded by the KIAA0319L gene, as an essential entry receptor for internalization into the host cell (Pillay et al., 2016). This dual-receptor mechanism is a critical determinant of AAV9's potent liver tropism and its unique ability to cross the blood-brain barrier (Zincarelli et al., 2008). In the context of gene therapy, these surface components are targeted by engineered AAV9 vectors to deliver therapeutic genetic material for treating various monogenic disorders, such as spinal muscular atrophy. Understanding the density and distribution of these glycans and receptors is vital for optimizing vector design and predicting clinical efficacy. However, the widespread expression of these targets can lead to off-target effects and necessitates careful monitoring of liver function and systemic immune responses during treatment (Manno et al., 2006).

Other names

KIAA0319LAAV receptorTerminal galactose residuesN-linked galactoseAAV9 receptor complex

AAV9 capsids utilize terminal galactose residues on hepatocyte surface glycans for initial attachment and sequestration in the liver (Bell et al., 2011). Following attachment, the virus interacts with the Adeno-associated virus receptor (AAVR), encoded by the KIAA0319L gene, which serves as an essential proteinaceous receptor for internalization and trafficking through the endosomal pathway (Pillay et al., 2016).