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Host cell surface receptors and glycans mediating AAV9 capsid entry

Molecular classification
Receptor, Glycan, G protein-coupled receptor, Cell surface protein
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Overview

The target 'Host cell surface receptors and glycans mediating AAV9 capsid entry' refers to the collective group of host molecules required for the cellular internalization of Adeno-associated virus serotype 9 (AAV9). The primary attachment factor for AAV9 is terminal N-linked galactose (specifically beta-1,4-galactose), which mediates initial docking to the cell surface (Bell et al., 2011; Shen et al., 2011). Following attachment, AAV9 requires the Adeno-associated virus receptor (AAVR, also known as KIAA0319L), a transmembrane protein that is essential for the transduction of most AAV serotypes (Pillay et al., 2016). Additionally, G protein-coupled receptor 108 (GPR108) has been identified as a critical, highly conserved entry factor for AAV9 and other serotypes, facilitating trafficking to the nucleus (Dudek et al., 2020). Other factors, such as the 37/67 kDa laminin receptor (RPSA) and certain integrins, may also play roles in the entry process (Akache et al., 2006; Asokan et al., 2006). These receptors are the primary targets for engineering AAV9-based gene therapy vectors, such as onasemnogene abeparvovec (Zolgensma), to improve tissue specificity and overcome barriers like the blood-brain barrier (Mendell et al., 2017). Understanding the distribution and density of these receptors is crucial for predicting the biodistribution and efficacy of AAV9-mediated gene delivery (Shen et al., 2012).

Other names
AAV9 entry factorsAAV9 receptorsAAV9 attachment factorsAAV9 entry complex
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Mechanism of action

AAV9 capsids bind to terminal N-linked galactose for attachment and Adeno-associated virus receptor (AAVR) for internalization, followed by GPR108-mediated trafficking to the nucleus.

03

Biological functions

Viral entryCell adhesionEndocytosisIntracellular trafficking
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Disease associations

InfectionGenetic disease
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Safety considerations

Off-target transductionLiver sequestrationImmune response to AAV capsidPre-existing anti-AAV9 antibodies
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Interacting drugs

Onasemnogene abeparvovec

1 more in the full profile.

07

Biomarkers

Terminal galactose expressionAAVR (KIAA0319L) expression levelGPR108 expression level

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