Adeno-associated virus receptor (AAVR) and cell-surface glycans (AAVR)

The Adeno-associated virus receptor (AAVR), also known as KIAA0319L, is a type I transmembrane protein identified as a universal and essential entry factor for most adeno-associated virus (AAV) serotypes (Pillay et al., 2016, Nature). It functions as a multi-domain receptor where specific Polycystic Kidney Disease (PKD) domains interact with the viral capsid to facilitate internalization. This process is preceded by the virus's attachment to cell-surface N-linked glycans, which serve as primary docking sites. For instance, AAV9 specifically binds to terminal galactose (Bell et al., 2011, Journal of Virology), while serotypes like AAV1, AAV5, and AAV6 utilize sialic acid linkages (Murlidharan et al., 2014, Frontiers in Microbiology). Together, these glycans and AAVR form a critical entry complex that determines the tissue tropism and transduction efficiency of AAV-based gene therapies. Currently, this complex is the primary target for several FDA-approved gene therapies, including Onasemnogene abeparvovec and Voretigene neparvovec, which leverage these pathways to deliver functional genes into target cells. Understanding the density and distribution of these receptors is essential for overcoming therapeutic challenges such as pre-existing immunity and off-target effects.

Other names

KIAA0319LKIAA0319-like proteinAAV receptorSialic acid-binding receptorGalactose-binding receptorAAVR-glycan complex

Facilitates viral capsid attachment to the cell membrane via glycan interactions followed by AAVR-mediated endosomal internalization for gene delivery.