Adeno-associated virus serotype 9 capsid protein (AAV9 capsid)

The Adeno-associated virus serotype 9 (AAV9) capsid is a protein shell composed of VP1, VP2, and VP3 subunits that encapsulates a single-stranded DNA genome for gene therapy delivery. It is distinguished by its unique ability to cross the blood-brain barrier and its broad tissue tropism, particularly for the central nervous system, heart, and liver (Bell et al., 2011; Shen et al., 2011). AAV9 initiates cellular entry by binding to N-linked terminal galactose residues on cell-surface glycoproteins, which serve as its primary attachment factor (Pillay et al., 2016). Following attachment, the capsid interacts with the adeno-associated virus receptor (AAVR/KIAA0319L) to facilitate endocytosis and subsequent nuclear trafficking. In clinical practice, the AAV9 capsid is the delivery vehicle for Onasemnogene abeparvovec, the first systemic gene therapy approved for spinal muscular atrophy. Key challenges include pre-existing neutralizing antibodies that can block transduction and dose-dependent toxicities such as hepatotoxicity and thrombotic microangiopathy (Bioworld, 2024; NIH, 2021).

Other names

AAV9 VP1/VP2/VP3AAV9 shellAAV-9 capsidAdeno-associated virus 9 capsidAAV9 viral protein

The AAV9 capsid facilitates the delivery of a therapeutic transgene into target cells by binding to N-linked terminal galactose residues on cell-surface glycoproteins, followed by internalization via the adeno-associated virus receptor (AAVR).