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Differential targeting of feline photoreceptors by recombinant adeno-associated viral vectors: implications for preclinical gene therapy trials

Gene Therapy volume 21, pages 913–920 (2014)Cite this article

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Abstract

The cat is emerging as a promising large animal model for preclinical testing of retinal dystrophy therapies, for example, by gene therapy. However, there is a paucity of studies investigating viral vector gene transfer to the feline retina. We therefore sought to study the tropism of recombinant adeno-associated viral (rAAV) vectors for the feline outer retina. We delivered four rAAV serotypes: rAAV2/2, rAAV2/5, rAAV2/8 and rAAV2/9, each expressing green fluorescent protein (GFP) under the control of a cytomegalovirus promoter, to the subretinal space in cats and, for comparison, mice. Cats were monitored for gene expression by in vivo imaging and cellular tropism was determined using immunohistochemistry. In cats, rAAV2/2, rAAV2/8 and rAAV2/9 vectors induced faster and stronger GFP expression than rAAV2/5 and all vectors transduced the retinal pigment epithelium (RPE) and photoreceptors. Unlike in mice, cone photoreceptors in the cat retina were more efficiently transduced than rod photoreceptors. In mice, rAAV2/2 only transduced the RPE whereas the other vectors also transduced rods and cones. These results highlight species differences in cellular tropism of rAAV vectors in the outer retina. We conclude that rAAV serotypes are suitable for use for retinal gene therapy in feline models, particularly when cone photoreceptors are the target cell.

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Acknowledgements

Funding for this study was provided by the Grousbeck Family Foundation, the Hal and Jean Glassen Memorial Foundation, the Myers Dunlap Endowment (to SMP-J) and research grants from the National Institutes of Health (8DP1EY023177 and 1R24EY019861 to JB, and T32OD011167 to Michigan State University), Foundation Fighting Blindness, and Research to Prevent Blindness. We would like to thank Janice Querubin and Lisa Allen for their assistance and animal care, and Cheryl Craft for providing the cone arrestin antibody.

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Authors and Affiliations

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

    A L Minella, F M Mowat, J T Bartoe & S M Petersen-Jones

  2. F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA

    K L Willett & J Bennett

  3. Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI, USA

    D Sledge

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  1. A L Minella
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Correspondence to S M Petersen-Jones.

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Minella, A., Mowat, F., Willett, K. et al. Differential targeting of feline photoreceptors by recombinant adeno-associated viral vectors: implications for preclinical gene therapy trials. Gene Ther 21, 913–920 (2014). https://doi.org/10.1038/gt.2014.65

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