Gene Therapy Rescues Cone Function in Congenital Achromatopsia
Human Molecular Genetics, 2010, Vol. 19, No. 13 2581–2593 doi:10.1093/hmg/ddq136 Advance Access published on April 8, 2010 Gene therapy rescues cone function in congenital achromatopsia Andra´s M. Koma´romy1,∗, John J. Alexander2,3,4, Jessica S. Rowlan1, Monique M. Garcia1,5, Vince A. Chiodo3, Asli Kaya5, Jacqueline C. Tanaka5, Gregory M. Acland6, William W. Hauswirth2,3 and Gustavo D. Aguirre1 1Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA, 2Department of Molecular Genetics and Microbiology and 3Department of Ophthalmology and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA, 4Vision Science Research Center, University of Alabama, Birmingham, AL 35294, USA, 5Department of Biology, Temple University, Philadelphia, PA 19122, USA and 6Baker Institute, Cornell University, Ithaca, NY 14853, USA Received January 19, 2010; Revised March 12, 2010; Accepted April 5, 2010 The successful restoration of visual function with recombinant adeno-associated virus (rAAV)-mediated gene replacement therapy in animals and humans with an inherited disease of the retinal pigment epithelium has ushered in a new era of retinal therapeutics. For many retinal disorders, however, targeting of therapeutic vec- tors to mutant rods and/or cones will be required. In this study, the primary cone photoreceptor disorder achro- matopsia served as the ideal translational model to develop gene therapy directed to cone photoreceptors. We demonstrate that rAAV-mediated gene replacement therapy with different forms of the human red cone opsin promoter led to the restoration of cone function and day vision in two canine models of CNGB3 achromatopsia, a neuronal channelopathy that is the most common form of achromatopsia in man.
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