Non-cardiac tissues transduced by Adeno-associated virus serotype 9

Non-cardiac tissues transduced by Adeno-associated virus serotype 9 (AAV9) refers to the systemic biodistribution of AAV9-based gene therapy vectors in organs such as the liver, skeletal muscle, and dorsal root ganglia. While AAV9 is frequently utilized for its ability to cross the blood-brain barrier and target the central nervous system or heart, it exhibits a broad natural tropism that leads to significant off-target accumulation (Foust et al., 2009). This transduction is primarily mediated by the interaction of the AAV9 capsid with terminal galactose residues and the universal AAV receptor (AAVR) (Bell et al., 2011; Pillay et al., 2016). In clinical settings, high-dose systemic administration of AAV9 vectors, such as Onasemnogene abeparvovec, has been associated with severe hepatotoxicity and elevated liver enzymes, necessitating the use of prophylactic corticosteroids (Mendell et al., 2017). Furthermore, preclinical studies in non-human primates have identified AAV9-mediated inflammation of the dorsal root ganglia, which can lead to sensory neuronopathy (Hinderer et al., 2018). Monitoring the transduction of these non-target tissues is a critical component of safety assessments in the development of AAV-delivered therapeutics.

Other names

Off-target AAV9 transductionPeripheral AAV9 biodistributionAAV9 non-cardiac tropismSystemic AAV9 distribution

AAV9 vectors enter non-cardiac cells by binding to terminal galactose residues on surface glycoproteins and utilizing the Adeno-associated virus receptor (AAVR) for internalization and intracellular trafficking (Bell et al., 2011; Pillay et al., 2016).