Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina

Recombinant adeno-associated virus (rAAV) is a promising vector for therapy of retinal degenerative diseases. We evaluated the efficiency, cellular sp ecificity, and safety of retinal cell transduction in nonhuman primates aft er subretinal delivery of an rAAV carrying a cDNA encoding green fluorescen t protein (EGFP), rAAV.CMV.EGFP. The treatment results in efficient and sta ble EGFP expression lasting >1 year. Transgene expression in the neural ret ina is limited exclusively to rod photoreceptors. There is neither electror etinographic nor histologic evidence of photoreceptor toxicity. Despite sig nificant serum antibody responses to the vector, subretinal readministratio n results in additional transduction events. The findings further character ize the retinal cell tropism of rAAV, They also support the development of studies aimed ultimately at treating inherited retinal degeneration by usin g rAAV-mediated gene therapy.