Adeno-associated virus receptor (AAVR) and terminal galactose (AAVR/Gal)

Adeno-associated virus serotype 9 (AAV9) utilizes a specific set of cell-surface molecules to achieve efficient cellular entry, most notably terminal N-linked galactose and the Adeno-associated virus receptor (AAVR). Terminal galactose serves as the primary attachment factor, and its presence on the vascular endothelium is a key determinant of AAV9's unique ability to cross the blood-brain barrier (Bell et al., 2011, Journal of Virology). Following attachment, the AAV9 capsid interacts with AAVR (encoded by the KIAA0319L gene), a transmembrane protein that is essential for the endocytosis and intracellular trafficking of the virus toward the nucleus (Pillay et al., 2016, Nature). Additionally, the 37/67 kDa laminin receptor (RPSA) has been identified as a co-receptor that may further stabilize these interactions (Akache et al., 2006, Gene Therapy). These molecular targets are the foundation for AAV9-based gene therapies, such as Onasemnogene abeparvovec, which is used to treat spinal muscular atrophy by delivering a functional SMN1 gene. However, the broad expression of these receptors can lead to significant off-target effects, particularly liver toxicity, and pre-existing antibodies in the population can neutralize the vector before it reaches its target tissue (Mendell et al., 2017, NEJM).

Other names

KIAA0319-like proteinKIAA0319LN-linked galactose37/67 kDa laminin receptorRPSAAAV9 receptor complex

The AAV9 capsid utilizes a dual-receptor mechanism where it first attaches to terminal N-linked galactose residues on the cell surface and subsequently interacts with the Adeno-associated virus receptor (AAVR) to undergo endocytosis and retrograde transport to the nucleus.