Adeno-associated virus receptor (AAVR) and Heparan sulfate proteoglycans (HSPGs) (AAVR/HSPG)

Heparan sulfate proteoglycans (HSPGs) and the Adeno-associated virus receptor (AAVR, also known as KIAA0319L) are the primary cellular components required for the attachment and entry of Adeno-associated viruses (AAV) into host cells (Summerford & Samulski, 1998, Journal of Virology; Pillay et al., 2016, Nature). HSPGs, which include syndecans and glypicans, serve as initial attachment factors that concentrate the virus on the cell surface through electrostatic interactions with the viral capsid (Kern et al., 2003, Journal of Virology). Following this initial docking, AAVR acts as a critical proteinaceous receptor essential for the internalization and productive intracellular trafficking of most AAV serotypes toward the nucleus (Dudek et al., 2018, Molecular Therapy). This dual-receptor mechanism is a fundamental determinant of viral tropism and is extensively exploited in the development of recombinant AAV (rAAV) gene therapies (Menzinsky et al., 2021, Frontiers in Molecular Neuroscience). By understanding the structural basis of these interactions, researchers can engineer synthetic capsids to improve delivery efficiency and tissue specificity for treating genetic disorders (Huang et al., 2019, Nature Communications). Currently, several FDA-approved gene therapies, such as Zolgensma and Luxturna, rely on these pathways to deliver therapeutic genetic material to target cells (FDA, 2019, Zolgensma Prescribing Information).

Other names

KIAA0319LKIAA0319-like proteinDyslexia-associated protein KIAA0319-likeHSPGSyndecanGlypicanPerlecanAAVR

Adeno-associated virus (AAV) vectors utilize Heparan sulfate proteoglycans (HSPGs) for initial cell surface attachment, followed by high-affinity binding to the Adeno-associated virus receptor (AAVR) which facilitates endocytosis and intracellular trafficking to the nucleus (Pillay et al., 2016, Nature; Summerford & Samulski, 1998, Journal of Virology).