Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration

Gene supplementation therapy for recessive forms of inherited retinal dystrophies

“…30 For more on novel AAV vectors for retinal gene therapy see the review by Vandenberghe and Auricchio. 33 EARLY PROOF-OF-PRINCIPLE FOR GENE SUPPLEMENTATION THERAPY FOR RETINAL DYSTROPHY Although earlier studies had shown limited efficacy of gene supplementation in the Rd1 murine model of retinal degeneration, which has a defect in the Pde6b gene, [34][35][36][37] the first definitive proof-of-concept for gene supplementation therapy for a photoreceptor cell defect was demonstrated in the Rds mouse, which has a naturally occurring null mutation in the Prph2 gene. 38,39 Subretinal injection of AAV2 carrying the murine Prph2 gene under control of the bovine rhodopsin promoter results in expression of the structural outer segment protein Peripherin 2 and the formation of photoreceptor cell outer segments that are otherwise absent in this mouse model.…”

Gene therapy for optic nerve disease

“…The recombinant form of AAV, commonly used for gene therapy experiments, is rep deficient meaning that it cannot replicate within the host cell. AAV vectors can be used to transfect a variety of ocular cell types including photoreceptors, [10][11][12] retinal pigment epithelial cells, 10,13,14 Muller cells, 15 and retinal ganglion cells (RGC). 16,17 Little ocular inflammation is induced and expression in RGC can persist for at least 1 year, raising hopes that AAV could be useful in the treatment of human optic nerve disease.…”

“…Correction of a specific ocular genetic defect requires gene delivery directly to the defective cells and has been successfully used to slow photoreceptor loss in rodent models of primary photoreceptor disease. 12,[23][24][25] As an example, AAV vectors have recently been used to restore photoreceptor structure and function in retinal degeneration slow (rds) mice. 26 These mice have a mutation in the Prph2 gene and mutations in this gene have also been demonstrated in human retinitis pigmentosa.…”

Gene therapy in the CNS

“…234 The PDE gene has been delivered to the subretinal space using both AAV and Ad vector. 76,235,236 The use of Ad vectors to deliver PDE gene resulted in a shorter (6 weeks) therapeutic effect 235 compared with the use of gutless Ad vectors (12 weeks). 76 The transient expression of the PDE gene using Ad vector probably results, in part, from immune response to viral antigens.…”