Adeno-associated virus serotype 8 cell-surface entry receptor (AAV8 receptor)

Adeno-associated virus serotype 8 (AAV8) cell-surface entry receptors are a group of host proteins that facilitate the attachment, internalization, and intracellular trafficking of AAV8 viral vectors. The primary attachment receptor is the 37/67-kDa Laminin Receptor (LamR, also known as RPSA), which mediates the initial binding of the AAV8 capsid to the cell surface (Akache et al., 2006). Productive infection further requires the Adeno-associated virus receptor (AAVR, or KIAA0319L), a universal proteinaceous receptor for most AAV serotypes that is essential for endosomal escape and trafficking (Pillay et al., 2016). Additionally, GPR108 has been identified as a critical entry factor localized to the trans-Golgi network that supports the post-entry movement of the virus toward the nucleus (Dudek et al., 2020). These receptors determine the strong liver tropism and high transduction efficiency of AAV8-based therapeutics, making them central to the delivery of gene therapies for monogenic disorders. Recombinant AAV8 vectors, such as those used in clinical trials for Hemophilia B (e.g., AAV8-hFIX) and metabolic diseases like Ornithine Transcarbamylase deficiency (DTX301), interact with these receptors to deliver therapeutic genes (Nathwani et al., 2011). Challenges associated with these receptors include pre-existing neutralizing antibodies in patients and the potential for liver toxicity at high vector doses. Understanding these receptor interactions is crucial for optimizing vector design and improving the safety and efficacy of AAV8-mediated gene transfer.

Other names

37/67-kDa Laminin ReceptorRPSALamRAdeno-associated virus receptorAAVRKIAA0319LGPR108G protein-coupled receptor 108

Binding of the AAV8 capsid to cell-surface attachment factors (LamR) and the essential proteinaceous receptor (AAVR) to initiate receptor-mediated endocytosis, followed by GPR108-facilitated trafficking through the trans-Golgi network to the nucleus for transgene delivery.