Adeno-associated virus receptor (AAVR) and hepatocyte-associated glycans (AAVR/Glycan complex)

The Adeno-associated virus receptor (AAVR), also known as KIAA0319L, is a critical transmembrane protein required for the cellular entry of most adeno-associated virus (AAV) serotypes (Pillay et al., Nature, 2016). On the surface of hepatocytes, AAVR works in conjunction with liver-associated glycans, such as heparan sulfate proteoglycans (HSPGs) for AAV2 or terminal galactose residues for AAV9, which serve as primary attachment factors (Summerford & Samulski, J. Virol., 1998). This receptor-glycan complex facilitates the initial binding of AAV capsids to the cell surface and their subsequent internalization via endocytosis. In the context of gene therapy, this interaction is the primary determinant of liver tropism for various AAV-based vectors, including AAV2, AAV5, and AAV8 (Bell et al., J. Virol., 2011). Understanding this target is essential for optimizing the delivery of therapeutic genes to the liver and for managing potential immune responses or off-target effects. Drugs interacting with this complex are primarily AAV-delivered gene therapies designed to treat hemophilia, spinal muscular atrophy, and other genetic disorders (FDA, 2023). Notable safety concerns include hepatotoxicity, often manifested as elevated liver enzymes, and the presence of pre-existing neutralizing antibodies that can block the interaction between the AAV capsid and the AAVR/glycan complex (Mingozzi & High, Nature Reviews Genetics, 2011).

Other names

KIAA0319LKIAA0319-like proteinHepatocyte surface glycansAAV receptor complexHSPG-AAVR complex

Facilitates viral capsid attachment to the cell surface via glycans followed by AAVR-mediated internalization and nuclear trafficking.