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

AAV-DJ is a synthetic adeno-associated virus (AAV) capsid created through DNA shuffling of AAV2, AAV8, and AAV9, designed for high-efficiency gene delivery (Grimm et al., 2008, Journal of Virology). Its entry into host cells is mediated by a dual-receptor system involving primary attachment to cell-surface glycans and subsequent interaction with a proteinaceous receptor. Specifically, AAV-DJ utilizes Heparan Sulfate Proteoglycans (HSPG) for initial docking on the cell membrane, a trait inherited from its AAV2 parent (Grimm et al., 2008). Following attachment, the capsid interacts with the Adeno-associated virus receptor (AAVR), also known as KIAA0319L, which is an essential host factor for the internalization and trafficking of most AAV serotypes, including AAV-DJ (Pillay et al., 2016, Nature). This receptor-mediated pathway is critical for the high transduction efficiency observed in hepatic tissues and various cell lines (Zhang et al., 2019, Journal of Virology). Understanding these interactions is vital for optimizing AAV-DJ-based gene therapies and managing potential off-target effects or neutralizing antibody interference. The presence and density of these receptors on the target cell surface directly influence the vector's therapeutic index and tissue specificity.

Other names

KIAA0319LHeparan sulfateHSPGAAV receptorAAVRAAV-DJ receptor complex

The AAV-DJ capsid facilitates gene delivery by first attaching to cell-surface Heparan Sulfate Proteoglycans (HSPG) and subsequently binding to the Adeno-associated virus receptor (AAVR/KIAA0319L) to trigger receptor-mediated endocytosis and nuclear translocation.