title: Prospects for retinal cone-targeted gene therapy.
abstract: Gene therapy strategies that target therapeutic genes to retinal cones are a worthy goal both because cone photoreceptor diseases are severely vision limiting and because many retinal diseases that do not affect cones directly eventually lead to cone loss, the reason for eventual blindness. Human achromatopsia is a genetic disease of cones that renders them nonfunctional but otherwise intact. Thus, animal models of achromatopsia were used in conjunction with adeno-associated virus (AAV) vectors whose serotype efficiently transduces cones and with a promoter that limits transgene expression to cones. In the Gnat2(cpfl3) mouse model of one genetic form of human achromatopsia, we were able to demonstrate recovery of normal cone function and visual acuity after a single subretinal treatment of vector that supplied wild-type Gnat2 protein to cones. This validates the overall strategy of targeting cones using recombinant viral vectors and justifies a more complete examination of animal models of cone disease as a prelude to considering a clinical gene therapy trial.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Alexander
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
mesh_terms: D000818:Animals; D003117:Color Vision Defects / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D020962:Heterotrimeric GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D019076:Transgenes
chemical_list: C515337:Gnat2 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins