Cell-surface attachment factors for adeno-associated virus capsid (AAV attachment factors)

Cell-surface attachment factors for adeno-associated virus (AAV) capsids are a diverse class of molecules, primarily glycans and proteoglycans, that mediate the initial, low-affinity binding of the virus to the host cell surface. These factors, which include heparan sulfate proteoglycans (HSPG), sialic acid, and galactose, serve to sequester and concentrate AAV particles at the plasma membrane, facilitating subsequent interactions with high-affinity entry receptors such as the universal AAV receptor (AAVR/KIAA0319L). The specific attachment factor utilized is a primary determinant of the tissue tropism and transduction efficiency of different AAV serotypes; for example, AAV2 and AAV3 utilize HSPG, while AAV1 and AAV5 target sialic acid, and AAV9 binds to terminal galactose. In the field of gene therapy, these factors are critical targets for capsid engineering aimed at redirecting viral delivery to specific tissues or evading pre-existing neutralizing antibodies. While AAV is non-pathogenic, the ubiquitous nature of these attachment factors can lead to therapeutic challenges, such as the sequestration of vectors in the liver or other non-target organs. Understanding and modulating these interactions is essential for optimizing the safety and efficacy of recombinant AAV (rAAV) products.

Other names

Heparan sulfate proteoglycanHSPGSialic acidGalactoseAAV primary receptorsGlycan attachment factorsN-linked glycansO-linked glycans

Competitive inhibition of viral binding to cell surface glycans or enzymatic removal of glycan moieties to prevent viral attachment.