Adeno-associated virus serotype 9 cell-surface entry receptors (AAV9 receptors)

Adeno-associated virus serotype 9 (AAV9) cell-surface entry receptors and glycans are the molecular components on host cells that facilitate the attachment and internalization of AAV9-based viral vectors. The primary attachment factor for AAV9 is terminal N-linked galactose, specifically with beta-galactose linkages, which allows the virus to bind to a wide variety of tissues, including the central nervous system, heart, and skeletal muscle. Following initial attachment, AAV9 utilizes the adeno-associated virus receptor (AAVR), also known as KIAA0319L, as an essential protein receptor for productive infection and intracellular trafficking. AAV9 is uniquely capable of crossing the blood-brain barrier via receptor-mediated transcytosis, a property that has made it the preferred vehicle for delivering therapeutic genes to the brain and spinal cord. This receptor system is the target for several gene therapies, most notably Onasemnogene abeparvovec (Zolgensma), which is used to treat spinal muscular atrophy by delivering a functional SMN1 gene. Despite its therapeutic utility, challenges include pre-existing neutralizing antibodies against the AAV9 capsid and potential safety concerns such as hepatotoxicity and dorsal root ganglia toxicity.

Other names

AAV9 cell-surface entry receptors/glycansTerminal N-linked galactoseAdeno-associated virus receptorAAVRKIAA0319LLaminin receptorLR37/67-kDa laminin receptor

Receptor-mediated viral entry and gene delivery