Unspecified hepatocyte cell surface receptor mediating AAVrh74 liver uptake

The unspecified hepatocyte cell surface receptor mediating AAVrh74 liver uptake is a functional target representing the primary protein or glycan on the surface of liver cells that facilitates the entry of AAVrh74 viral vectors. AAVrh74 is a rhesus-derived adeno-associated virus serotype utilized in systemic gene therapies, most notably delandistrogene moxeparvovec (Elevidys) for Duchenne Muscular Dystrophy (DMD). Although AAVrh74 exhibits strong tropism for skeletal and cardiac muscle, it also demonstrates a high propensity for liver uptake, which acts as a sink for systemically administered doses. This sequestration necessitates the use of high viral loads to achieve therapeutic levels in muscle, which in turn increases the risk of severe adverse events such as acute liver failure, transaminitis, and systemic inflammatory responses. While the exact molecular identity of this receptor is currently unspecified or under investigation, candidates include the 37/67-kDa laminin receptor (LamR), the universal AAV receptor (AAVR/KIAA0319L), and potentially galactose-binding receptors like the asialoglycoprotein receptor (ASGPR). Engineering AAVrh74 capsids to de-target this receptor is a critical strategy for improving the safety and efficacy of gene therapies.

Other names

Hepatocyte AAVrh74 receptorAAVrh74 liver uptake receptorAAVrh74 liver sink receptorAAVrh74 hepatocyte binding factor

Mediates the binding and internalization of AAVrh74-based gene therapy vectors into hepatocytes, leading to liver sequestration and potential hepatotoxicity.