In utero gene therapy rescues vision in a murine model of congenital blindness

Nadine S. Dejneka, Enrico M. Surace, Tomas S. Aleman, Artur V. Cideciyan, Arkady Lyubarsky, Andrey Savchenko, T. Michael Redmond, Waixing Tang, Zhangyong Wei, Tonia S. Rex, Ernest Glover, Albert M. Maguire, Edward N Pugh Jr, Samuel G. Jacobson, Jean Bennett

Research output: Contribution to journalArticlepeer-review

173 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)182-188
Number of pages7
JournalMolecular Therapy
Issue number2
StatePublished - Feb 2004
Externally publishedYes


  • Adeno-associated virus
  • Gene therapy
  • Genetic disease
  • In utero therapy
  • Mouse model
  • Neurodegeneration
  • Phototransduction
  • Retina
  • Retinal degeneration
  • Viral gene transfer

ASJC Scopus subject areas

  • Molecular Biology


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