Adeno-associated virus receptor (AAVR) (AAVR)

The Adeno-associated virus receptor (AAVR), encoded by the KIAA0319L gene, is a critical type I transmembrane protein that serves as the essential entry receptor for multiple adeno-associated virus (AAV) serotypes, including AAV5 (Pillay et al., 2016; PMID: 26814968). In hepatocytes, the AAV5 capsid uniquely engages the first polycystic kidney disease (PKD1) domain of AAVR, a distinct mechanism compared to other serotypes like AAV2 which utilize the PKD2 domain (Zhang et al., 2019; PMID: 30742071). Beyond AAVR, AAV5 entry is facilitated by initial attachment to 2,3-linked sialic acid and interaction with co-receptors such as platelet-derived growth factor receptors (PDGFR-alpha and PDGFR-beta) (Di Pasquale et al., 2003; PMID: 12857914). This receptor complex is the primary gateway for AAV5-based gene therapies, such as etranacogene dezaparvovec (Hemgenix) for Hemophilia B and valoctocogene roxaparvovec (Roctavian) for Hemophilia A, which leverage the vector's natural liver tropism to deliver therapeutic genes. Clinical efficacy is often limited by pre-existing neutralizing antibodies against the AAV5 capsid, and safety monitoring typically focuses on immune-mediated hepatotoxicity, characterized by elevated liver enzymes. Understanding the interaction between the AAV5 capsid and these hepatocyte surface receptors is vital for optimizing vector design and patient selection in gene therapy protocols.

Other names

KIAA0319LKIAA0319-like proteinPlatelet-derived growth factor receptor alpha (PDGFRA)Platelet-derived growth factor receptor beta (PDGFRB)2,3-linked sialic acidHepatocyte cell surface receptors for AAV5 capsid

The AAV5 capsid binds to the Adeno-associated virus receptor (AAVR), specifically interacting with its PKD1 domain, and utilizes co-receptors such as PDGFR and sialic acid to mediate endocytosis and entry into hepatocytes for transgene delivery.