Long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates.
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.
Lebherz
Corinna
C
Gene Therapy Program, Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Auricchio
Alberto
A
Maguire
Albert M
AM
Rivera
Victor M
VM
Tang
Waixing
W
Grant
Rebecca L
RL
Clackson
Tim
T
Bennett
Jean
J
Wilson
James M
JM
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
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D004921:Erythropoietin; D020123:Sirolimus