Adeno-associated virus receptor (AAVR) and cell-surface sialic acid glycans (AAVR/Sialic Acid)

The Adeno-associated virus receptor (AAVR) and cell-surface sialic acid glycans constitute the primary entry machinery for the AAVrh.10 serotype, a rhesus-derived viral vector frequently used in gene therapy. AAVrh.10 initiates infection by attaching to alpha-2,3- and alpha-2,6-linked sialic acid residues on the host cell surface, which act as essential attachment factors (Mietzsch et al., 2014). Following this initial tethering, the viral capsid interacts with AAVR (KIAA0319L), a transmembrane protein that facilitates the internalization and endosomal escape of the virus (Pillay et al., 2016). This interaction is a critical determinant of the vector's high tropism for the central nervous system and liver, making it a preferred vehicle for treating neurological and metabolic disorders. In clinical settings, AAVrh.10-based drugs like RGX-121 target these receptors to deliver therapeutic genes for conditions such as Mucopolysaccharidosis Type II (MPS II). However, the efficacy of targeting these receptors can be limited by pre-existing neutralizing antibodies in the human population and potential off-target sequestration in the liver. Understanding the molecular details of this receptor complex is vital for optimizing vector design and improving patient outcomes in gene therapy.

Other names

KIAA0319LAAV receptorAlpha-2,3-linked sialic acidAlpha-2,6-linked sialic acidN-linked sialic acidAAVrh.10 attachment factors

Viral capsid binding to sialic acid attachment factors followed by AAVR-mediated endocytosis and nuclear translocation for transgene expression.