AAV3-Stab2-huFVIII

AAV3-Stab2-huFVIII is an experimental gene therapy candidate designed for the treatment of hemophilia A. It utilizes an adeno-associated virus serotype 3 (AAV3) vector to deliver a B-domain-deleted human Factor VIII (huFVIII) transgene. Uniquely, the expression of huFVIII is driven by a Stabilin 2 (Stab2) promoter, which is specific to liver sinusoidal endothelial cells (LSECs). This approach aims to mimic the natural site of FVIII synthesis and secretion in the liver, potentially overcoming the limitations of hepatocyte-directed gene therapies, such as transient expression or cellular stress. Preclinical studies have demonstrated that the AAV3-Stab2-huFVIII construct achieves specific and dose-dependent expression in human LSEC lines while remaining restricted in hepatocytes.