title: Long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates.
abstract: Adeno-associated viral gene therapy has shown promise for the treatment of inherited and degenerative diseases in a variety of animal models. Some of the most dramatic results have been obtained in the field of ocular gene therapy, where efficacy has been tremendous in inherited and acquired retinal disorders. For the promise of this approach to be realized it will be necessary to create vectors capable of pharmacologic or physiologic regulation of the transgene. We describe in this paper a dimerizer-inducible viral expression system that is able to reproducibly drive expression of the reporter gene erythropoietin in the eyes of nonhuman primates over a period of 2.5 years. The expression profiles were characterized by minimal basal expression in the absence of inducer and dose-responsive maximal expression in the presence of inducer drug.
authors.affiliation: Gene Therapy Program, Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Corinna
authors.initials: C
authors.lastname: Lebherz
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.forename: Victor M
authors.initials: VM
authors.lastname: Rivera
authors.forename: Waixing
authors.initials: W
authors.lastname: Tang
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Grant
authors.forename: Tim
authors.initials: T
authors.lastname: Clackson
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D004921:Erythropoietin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005123:Eye / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008253:Macaca mulatta; D020123:Sirolimus / Q000494:pharmacology; D019076:Transgenes / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D004921:Erythropoietin; D020123:Sirolimus