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Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

Gene Therapy volume 18, pages 53–61 (2011)Cite this article

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Abstract

The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65−/− dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85–180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65−/− dog. This finding has important implications for the treatment of human LCA type II patients.

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Acknowledgements

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 Wellcome Trust Advanced Fellow. RRA and JWB are investigators at The NIHR Centre for Ophthalmology at UCl and Moorfields Eye Hospital. We acknowledge Janice Querubin for providing veterinary technician expertise in all aspects of handling and caring for the dogs and Cheri Johnson for assistance with canine reproduction.

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Authors and Affiliations

  1. Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA

    M J Annear, J T Bartoe & S M Petersen-Jones

  2. Department of Genetics, UCL Institute of Ophthalmology, London, UK

    S E Barker, A J Smith, J W Bainbridge & R R Ali

  3. Center for Statistical Consulting, Michigan State University, East Lansing, MI, USA

    P G Curran

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  1. M J Annear
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Correspondence to R R Ali or S M Petersen-Jones.

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Annear, M., Bartoe, J., Barker, S. et al. Gene therapy in the second eye of RPE65-deficient dogs improves retinal function. Gene Ther 18, 53–61 (2011). https://doi.org/10.1038/gt.2010.111

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