This gene therapy delivers a transgene encoding the Retinal Protective Factor-2 (RPF-2) protein that is easy to regulate and provides broad-spectrum protection against retinal degeneration. Retinal degenerations are diseases characterized by the irreversible loss of light-sensitive photoreceptors, causing vision impairment in 9.1 million people in the United States . While an attractive treatment option is delivery of broad-spectrum neuroprotective factors through gene therapy, available therapies have limited clinical application due to their inability to control gene expression.
Researchers at the University of Florida have developed an AAV gene therapy for retinal degeneration that controls the expression of the protective protein using the antibiotic trimethoprim. By allowing for regulated protein expression, this gene therapy enables treatment of the broad range of mutations that cause retinal degeneration. Researchers have shown that stabilized RPF-2 can protect photoreceptors and prevent blindness in treated mice.
Gene therapy for broad-spectrum protection against retinal degeneration that utilizes an FDA-approved antibiotic to control gene expression
An adeno-associated virus vector delivers a synthetic gene encoding retinal protective factor 2 (RPF-2), a protein that expresses domains of leukemia inhibitory factor fused to the destabilization domain of bacterial dihydrofolate reductase. The FDA-approved antibiotic trimethoprim (TMP) regulates RPF-2 production; expression levels stabilize with the binding of TMP and reverse with TMP withdrawal. Regulated expression of stabilized RPF-2 protects photoreceptors and prevents blindness in individuals with retinal degeneration.