AAV-hOps-ArrGG

AAV-hOps-ArrGG is an adeno-associated virus (AAV) based gene therapy designed to treat inherited retinal degenerations (IRDs) by enhancing photoreceptor metabolism. It utilizes an AAV2 vector with multiple capsid modifications (Y272F, Y444F, Y500F, Y730F, and T491V) to deliver a modified version of arrestin1, termed ArrGG, under the control of the human opsin (hOps) promoter. Unlike wild-type arrestin1, which inhibits the glycolytic enzyme enolase1 by approximately 25%, ArrGG is engineered to retain binding to enolase1 without suppressing its catalytic activity. By relieving this metabolic brake, the therapy increases glycolytic output and lactate production in photoreceptors, providing a gene-agnostic neuroprotective strategy to preserve retinal structural integrity and functional vision across diverse genetic causes of IRD.