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AAVrh-10 transduces outer retinal cells in rodents and rabbits following intravitreal administration

Abstract

Recombinant adeno-associated virus (rAAV) has been widely used for gene delivery in animal models and successfully applied in clinical trials for treating inherited retinal disease. Although subretinal delivery of AAVs can effectively transduce photoreceptors and/or retinal pigmental epithelium (RPE), cells most affected by inherited retinal diseases, the procedure is invasive and complicated, and only delivers the gene to a limited retinal area. AAVs can also be delivered intravitreally to the retina, a much less invasive nonsurgical procedure. However, intravitreal administration of non-modified AAV serotypes tends to transduce only ganglion cells and inner nuclear layer cells. To date, most non-modified AAV serotypes that have been identified are incapable of efficiently transducing photoreceptors and/or RPE when delivered intravitreally. In this study, we investigate the retinal tropism of AAVrh10 vector administered by intravitreal injection to mouse, rat, and rabbit eyes. Our results demonstrate that AAVrh10 is capable of transducing not only inner retinal cells, but also outer retinal cells in all three species, though the transduction efficiency in rabbit was low. In addition, AAVrh10 preferentially transduced outer retinal cells in mouse models of retinal disease. Therefore, AAVrh10 vector could be a useful candidate to intravitreally deliver genes to photoreceptor and RPE cells.

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Acknowledgements

The authors wish to thank Dr. James M. Wilson (University of Pennsylvania, Philadelphia, Pennsylvania) for providing the AAVrh10 capsid DNA construct, Suja Hiriyanna for producing the AAVrh10-CMV-EGFP vector, Maria Santos and Jinbo Li for technical assistance, and Wei Li, Wenhan Yu for reviewing the paper. The research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Deafness and other Communication Disorders and the National Eye Institute.

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Correspondence to Ronald A. Bush.

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Zeng, Y., Qian, H., Wu, Z. et al. AAVrh-10 transduces outer retinal cells in rodents and rabbits following intravitreal administration. Gene Ther 26, 386–398 (2019). https://doi.org/10.1038/s41434-019-0094-3

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