AAV-FGF21-Zon

AAV-FGF21-Zon is a regulatable gene therapy designed to provide long-acting delivery of native fibroblast growth factor 21 (FGF21) for the treatment of metabolic disorders. The therapy utilizes an adeno-associated virus (AAV) vector to transduce skeletal muscle cells, which then serve as a long-lived biofactory to produce and secrete FGF21 protein into the bloodstream. A key feature of this asset is the Zon switch, an ultra-tight, self-cleavage-based RNA ON-switch that allows for precise control of gene expression. Expression is induced by the administration of a specific oligonucleotide trigger molecule, enabling dose titration and the ability to terminate expression if adverse events occur. In preclinical models (ob/ob mice), AAV-FGF21-Zon demonstrated significant improvements in body weight control, blood glucose levels, insulin sensitivity, and liver health, including a reduction in hepatic steatosis and markers of liver inflammation such as ALT and AST.