Cell-surface receptors and attachment factors recognized by the Adeno-associated virus (AAV) capsid

Cell-surface receptors and attachment factors recognized by the Adeno-associated virus (AAV) capsid comprise a diverse group of molecules that facilitate the entry of AAV vectors into host cells (Pillay et al., 2016). The primary and most universal protein receptor is the adeno-associated virus receptor (AAVR), also known as KIAA0319L, which is essential for the endocytosis and trafficking of most AAV serotypes (Nature, 2016). Initial binding is often mediated by attachment factors such as heparan sulfate proteoglycans (HSPG), sialic acid, or galactose, which concentrate the virus on the cell surface (J. Virol., 1998). Following attachment, the virus interacts with AAVR and potentially other co-receptors like GPR108, fibroblast growth factor receptor 1 (FGFR1), or the laminin receptor to trigger internalization (Molecular Therapy, 2018). These molecules are not traditional therapeutic targets for small molecules but are critical targets for the design and optimization of AAV-based gene therapy vectors like Onasemnogene abeparvovec (FDA, 2019). The efficiency of gene delivery is highly dependent on the expression levels of these receptors and the binding affinity of the engineered AAV capsid. Challenges in this field include pre-existing immunity to capsids and the need for cell-type-specific targeting to avoid off-target effects (Frontiers in Immunology, 2020). Consequently, research focuses on mapping the capsid-receptor interface to create next-generation vectors with improved clinical profiles.

Other names

AAV receptorsAAV attachment factorsAdeno-associated virus receptorAAVRKIAA0319LHeparan sulfate proteoglycanHSPGGPR108Laminin receptorFibroblast growth factor receptor 1Hepatocyte growth factor receptor

Viral vector binding to cell-surface attachment factors and high-affinity protein receptors followed by receptor-mediated endocytosis and retrograde trafficking to the nucleus.