Adeno-associated virus receptor and associated glycans (AAVR/Glycans)

The cell-surface receptors and glycans for AAV capsids are a diverse group of host cell molecules that facilitate the attachment and entry of adeno-associated virus (AAV) vectors used in gene therapy. Primary attachment is often mediated by glycans such as heparan sulfate proteoglycans (HSPG), sialic acid, or galactose, which vary in usage across different AAV serotypes (e.g., AAV2 uses HSPG, while AAV9 uses galactose). Following attachment, the adeno-associated virus receptor (AAVR), a type I transmembrane protein, serves as a near-universal entry receptor for most AAV variants by binding to the viral capsid and facilitating endocytosis. Other essential factors include GPR108, a G protein-coupled receptor-like protein localized in the trans-Golgi network, and various co-receptors like integrins and growth factor receptors that assist in intracellular trafficking. These receptors determine the tissue tropism and transduction efficiency of AAV-based drugs, such as voretigene neparvovec and onasemnogene abeparvovec. Engineering the interaction between the AAV capsid and these receptors is a primary strategy for developing next-generation gene therapies with enhanced specificity and reduced off-target effects.

Other names

Adeno-associated virus receptorAAVRKIAA0319LHeparan sulfate proteoglycanHSPGSialic acidGalactoseGPR108AAV attachment factorsAAV entry receptors

Viral capsid binding followed by receptor-mediated endocytosis and intracellular trafficking to the nucleus.