Adeno-associated virus 9 receptor complex

The Adeno-associated virus 9 (AAV9) receptor complex is a multi-component system on the host cell surface that facilitates the attachment and internalization of AAV9, a widely used vector in gene therapy [1, 2]. The primary attachment factor for AAV9 is terminal beta-D-galactose, a cell-surface glycan that distinguishes AAV9 from other serotypes that typically bind heparan sulfate or sialic acid [1, 4]. Following initial glycan binding, the virus engages the proteinaceous adeno-associated virus receptor (AAVR, also known as KIAA0319L), which is essential for the endocytosis and subsequent trafficking of the viral particles to the trans-Golgi network [2, 5]. Other factors, such as GPR108 and the 36/37 kDa laminin receptor, have also been identified as critical for efficient AAV9 entry and transduction [3, 4]. This receptor complex is a key determinant of AAV9's unique tissue tropism, including its notable ability to cross the blood-brain barrier and target the central nervous system and cardiac tissue [1, 3]. Consequently, these receptors are fundamental to the efficacy of AAV9-based therapeutics, such as onasemnogene abeparvovec, used for treating spinal muscular atrophy [5]. Understanding the distribution and density of these receptors across different tissues is vital for optimizing vector design and predicting clinical outcomes in gene therapy [2, 5].

Other names

Cell-surface glycans and associated AAV9 entry receptorsTerminal galactoseAdeno-associated virus receptor (AAVR)KIAA0319LGPR10836/37 kDa laminin receptor (LamR)

Facilitation of viral attachment and receptor-mediated endocytosis for transgene delivery