Journal
MOLECULAR THERAPY
Volume 9, Issue 2, Pages 182-188Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2003.11.013
Keywords
adeno-associated virus; retinal degeneration; retina; mouse model; gene therapy; neurodegeneration; in utero therapy; viral gene transfer; genetic disease; phototransduction
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Funding
- NEI NIH HHS [R01 EY10820, U10EY013729, EY13203, EY12156, EY13385, F32-EY07065, EY02660] Funding Source: Medline
- NIDDK NIH HHS [5-P30-DK-47747-10] Funding Source: Medline
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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.
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