Gene Augmentation Trials Using the Rpe65-Deficient Dog: Contributions Towards Development and Refinement of Human Clinical Trials

  • Simon M. Petersen-JonesEmail author
  • Matthew J. Annear
  • Joshua T. Bartoe
  • Freya M. Mowat
  • Susie E. Barker
  • Alexander J. Smith
  • James W. Bainbridge
  • Robin R. Ali
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)


Dogs with a spontaneous mutation in Rpe65 have been key in the testing of gene augmentation therapy using viral vectors to introduce a normal copy of the Rpe65 gene. These ground-breaking experiments have led to Phase I/II human clinical trials for treatment of Leber congenital amaurosis type II (LCAII).

The Rpe65-deficient dog remains a useful model for studies to refine this treatment approach. A recent question it has been used to answer is whether or not immune response resulting from the gene augmentation treatment of one eye interferes with the success of the same treatment in the second eye. Fortunately, it was shown that treatment of the second eye had a similar success to that of the first eye, clearly demonstrating potential for gene augmentation therapy in the second eye of LCAII patients.


Leber congenital amaurosis RPE65 Canine model Briard Gene therapy Gene augmentation AAV2 Immune response Repeated injection Subretinal injection 



This work was supported by the British Retinitis Pigmentosa Society, The Midwest Eye Banks and Transplantation Center Research Program and Michigan State University College of Veterinary Medicine Purebred Dog Endowment Fund. JWB is a Welcome Trust Advanced Fellow. RRA and JWB are investigators at The NIHR Centre for Ophthalmology at UCl and Moorfields Eye Hospital.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Simon M. Petersen-Jones
    • 1
    Email author
  • Matthew J. Annear
    • 1
  • Joshua T. Bartoe
    • 1
  • Freya M. Mowat
    • 1
  • Susie E. Barker
    • 2
  • Alexander J. Smith
    • 2
  • James W. Bainbridge
    • 2
  • Robin R. Ali
    • 2
  1. 1.Department of Small Animal Clinical SciencesMichigan State UniversityEast LansingUSA
  2. 2.Department of GeneticsUCL Institute of OphthalmologyLondonUK

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