Hepatocyte cell-surface receptors for AAV5

Hepatocyte cell-surface receptors for AAV5 are the molecular components on the surface of liver cells that facilitate the binding, entry, and transduction of Adeno-associated virus serotype 5 (AAV5) vectors. The primary proteinaceous receptor is the Adeno-associated virus receptor (AAVR), also known as KIAA0319L, which is a type I transmembrane protein essential for the entry of most AAV serotypes (Nature, 2016). AAV5 specifically interacts with the first polycystic kidney disease (PKD1) domain of AAVR to initiate internalization (Journal of Virology, 2017). Additionally, AAV5 utilizes N-linked sialic acid (specifically alpha-2,3- and alpha-2,6-linked) as an initial attachment factor and the Platelet-derived growth factor receptor (PDGFR, including both alpha and beta isoforms) as a co-receptor for efficient cellular entry (Nature Medicine, 2003; PNAS, 2000). These receptors are critical for the success of liver-directed gene therapies, as they determine the efficiency of transgene delivery to hepatocytes. Clinically approved AAV5-based therapies, such as etranacogene dezaparvovec for Hemophilia B and valoctocogene roxaparvovec for Hemophilia A, rely on these receptors to deliver functional genetic material to the liver (FDA, 2022). Understanding the expression and accessibility of these receptors is essential for optimizing vector dosing and managing potential safety concerns like immune-mediated hepatotoxicity. The low seroprevalence of AAV5 in the human population makes these receptors particularly attractive targets for gene therapy applications.

Other names

AAV5 receptorsAdeno-associated virus receptorAAVRKIAA0319LPlatelet-derived growth factor receptorPDGFRSialic acid receptors

Viral attachment and internalization via receptor-mediated endocytosis