1. ¹F.M. Kirby Center and Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104-2689, USA
2. ²Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, 6 Center Drive, MSC 2740, Bethesda, MD 20892-2740, USA

Correspondence: Jean Bennett, Fax: (215) 573-7155. E-mail: jebennet@mail.med.upenn.edu

^*These authors contributed equally to this work.

Received 30 October 2003; Accepted 20 November 2003.

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.