Adeno-associated virus 9 capsid – cell surface attachment factors (AAV9-AF)

Adeno-associated virus 9 (AAV9) capsid – cell surface attachment factors are the host molecules that facilitate the binding, entry, and intracellular trafficking of AAV9-based gene therapy vectors. The primary attachment factor is terminal N-linked galactose, which mediates the initial docking of the AAV9 capsid to the cell surface (Bell et al., 2011). Following attachment, the virus interacts with the adeno-associated virus receptor (AAVR, also known as KIAA0319L), a proteinaceous receptor essential for endocytosis and productive trafficking to the nucleus (Pillay et al., 2016). AAV9 is uniquely characterized by its ability to cross the blood-brain barrier, allowing for the treatment of neurological diseases via systemic administration (Creative Diagnostics). Therapeutic agents such as onasemnogene abeparvovec utilize these interactions to deliver functional genes to target tissues like motor neurons (AJMC, 2024). Clinical challenges associated with these factors include the presence of pre-existing neutralizing antibodies that can block viral entry and the risk of immune-mediated adverse events (Boutin et al., 2010). High-dose administration of AAV9 vectors is also associated with safety concerns such as hepatotoxicity, thrombotic microangiopathy, and dorsal root ganglion toxicity (Drug Discovery News, 2025).

Other names

AAV9 receptorsTerminal N-linked galactoseAdeno-associated virus receptorAAVRKIAA0319L37/67-kDa laminin receptorLamRN-linked glycans with terminal galactosyl residues

The AAV9 capsid binds to terminal N-linked galactose residues on the cell surface for initial attachment, followed by engagement with the essential proteinaceous receptor AAVR (KIAA0319L) to facilitate endocytosis and nuclear delivery of the therapeutic transgene.