Adeno-associated virus serotype 9 capsid–receptor interface (AAV9-receptor interface) (AAV9-receptor interface)

The Adeno-associated virus serotype 9 (AAV9) capsid–cell surface receptor interface is the molecular boundary where the AAV9 viral vector interacts with host cells to initiate gene delivery. This interface is characterized by the binding of the AAV9 capsid to terminal galactose residues on N-linked glycans, which act as the primary attachment factor (Bell et al., 2011, J. Clin. Invest.). Following attachment, the capsid interacts with the Adeno-associated virus receptor (AAVR, also known as KIAA0319L), a transmembrane protein essential for endocytosis and successful infection (Pillay et al., 2016, Nature). This specific interface is highly valued in gene therapy because it allows AAV9 to cross the blood-brain barrier and transduce neurons and cardiomyocytes effectively. Therapeutic agents like Onasemnogene abeparvovec (Zolgensma) utilize this interface to deliver functional genes to patients with spinal muscular atrophy (FDA, 2019). However, the interface is also the target of pre-existing neutralizing antibodies in humans, which can block vector entry and limit treatment eligibility. Engineering this interface is a primary strategy for developing next-generation vectors with improved tropism and reduced immunogenicity.

Other names

AAV9-Galactose interfaceAAV9-AAVR interactionAAV9-KIAA0319L interfaceAAV9 capsid-glycan interface

The interface facilitates viral attachment to terminal galactose residues and subsequent binding to the AAVR protein, triggering receptor-mediated endocytosis and nuclear delivery of the genetic payload (Bell et al., 2011; Pillay et al., 2016).