oa Editorial [Hot topic: AAV-Mediated Gene Therapy for the Treatment of Retinal Diseases (Guest Editor: Fabienne Rolling)]

This special issue was meant to provide a comprehensive review on AAV-mediated retinal gene therapy from vector design to current clinical applications. There has been a great progress over the past decade in generating and characterizing animal models for retinal disorders, developing and testing strategies for ameliorating the disease process and moving the promising proof-of-concept data into clinical trials. The recent success of three separate Phase I clinical trials investigating an AAV2/2 -mediated gene therapy for the treatment of Leber's Congenital Amaurosis (LCA) due to RPE65 mutations [1-4] provides a great incentive to extend these accomplishments to other retinal diseases. The strategy to treat autosomal recessive diseases, in which the mutated gene product is not existent or does not cause toxic effects, is to provide the cell with a correct allele of the mutated gene (ex : rpe65). The choice of vector and promoter for the expression cassette will depend on the targeted cells that is in most of the cases either the retinal pigmented epithelium (RPE) cells or the photoreceptors. The strategy to treat autosomal dominant diseases, which are caused by mutations which result in a toxic “gain of function” effect of the encoded protein (ex: Rhodopsin), is to suppress the production of the toxic protein using either ribozymes or siRNA in conjunction with efficient replacement. A third strategy consists in gene supply, which is the delivery of a gene that can prevent or arrest disease progression without being directly implicated in the disease pathogenesis. This approach involves antiapoptotic factors to prevent retina neurons degeneration (Retinitis Pigmentosa, LCA, glaucoma), and anti-angiogenic molecules to inhibit retinal neovascularization (age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity). These retinal gene transfer strategies as well as other considerations such as AAV vector design, AAV vector production, immune response and issues relating to clinical trials are discussed in this special issue. On behalf of the Current Gene Therapy journal, I would like to thank the authors for their outstanding articles that truly illustrate the impressive breakthroughs achieved in AAV-mediated gene therapies for the retina, including the first evidence of a therapeutic effect in humans.