Adeno-associated virus receptor (AAVR) and terminal galactose glycans (AAVR)

Adeno-associated virus serotype 9 (AAV9) utilizes a dual-receptor system for cellular entry, primarily involving the Adeno-associated virus receptor (AAVR, also known as KIAA0319L) and terminal N-linked galactose glycans. AAVR is a transmembrane protein containing five polycystic kidney disease (PKD) domains, with the PKD2 domain being essential for AAV9 binding and internalization. Terminal galactose serves as a primary attachment factor, facilitating the initial docking of the virus to the cell surface, particularly on the luminal side of brain microvascular endothelial cells. These interactions enable AAV9 to undergo transcytosis across the blood-brain barrier (BBB), allowing it to transduce neurons and astrocytes throughout the central nervous system (CNS). This unique capability has made AAV9 a cornerstone of gene therapy, most notably in the treatment of spinal muscular atrophy (SMA) with the FDA-approved drug Onasemnogene abeparvovec. However, therapeutic use is limited by challenges such as pre-existing neutralizing antibodies and the risk of systemic toxicity, including hepatotoxicity and thrombotic microangiopathy, at high doses.

Other names

KIAA0319LAAV receptorN-linked galactoseTerminal galactosyl residuesAAV9 receptorAAV9 entry factors

Viral vector binding to cell surface glycans and protein receptors followed by internalization and nuclear delivery of genetic material.