title: In utero gene therapy rescues vision in a murine model of congenital blindness.
abstract: The congenital retinal blindness known as Leber congenital amaurosis (LCA) can be caused by mutations in the RPE65 gene. RPE65 plays a critical role in the visual cycle that produces the photosensitive pigment rhodopsin. Recent evidence from human studies of LCA indicates that earlier rather than later intervention may be more likely to restore vision. We determined the impact of in utero delivery of the human RPE65 cDNA to retinal pigment epithelium cells in a murine model of LCA, the Rpe65(-/-) mouse, using a serotype 2 adeno-associated virus packaged within an AAV1 capsid (AAV2/1). Delivery of AAV2/1-CMV-hRPE65 to fetuses (embryonic day 14) resulted in efficient transduction of retinal pigment epithelium, restoration of visual function, and measurable rhodopsin. The results demonstrate AAV-mediated correction of the deficit and suggest that in utero retinal gene delivery may be a useful approach for treating a variety of blinding congenital retinal diseases.
authors.affiliation: F.M. Kirby Center and Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104-2689, USA.
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Dejneka
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Surace
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: Arkady
authors.initials: A
authors.lastname: Lyubarsky
authors.forename: Andrey
authors.initials: A
authors.lastname: Savchenko
authors.forename: T Michael
authors.initials: TM
authors.lastname: Redmond
authors.forename: Waixing
authors.initials: W
authors.lastname: Tang
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Wei
authors.forename: Tonia S
authors.initials: TS
authors.lastname: Rex
authors.forename: Ernest
authors.initials: E
authors.lastname: Glover
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.forename: Edward N
authors.initials: EN
authors.lastname: Pugh
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001766:Blindness / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D002352:Carrier Proteins; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D005136:Eye Proteins; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D014599:Uterus; D014785:Vision, Ocular / Q000235:genetics / Q000502:physiology*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase