Subretinal delivery of recombinant AAV serotype 8 vector in dogs results in gene transfer to neurons in the brain

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Stieger, Knut | Colle, Marie-Anne | Dubreil, Laurence | Mendes-Madeira, Alexandra | Weber, Michel | Le Meur, Guylène | Deschamps, Jack-Yves | Provost, Nathalie | Nivard, Delphine | Cherel, Yan | Moullier, Philippe | Rolling, Fabienne

Edité par CCSD ; Cell Press -

International audience. Recombinant adeno-associated virus (rAAV) vectors are among the most efficient gene delivery vehicles for gene transfer to the retina. This study evaluates the behavior of the rAAV8 serotype vector with regard to intraocular delivery in rats and dogs. Subretinal delivery of an AAV2/8.gfp vector results in efficient gene transfer in the retinal pigment epithelium (RPE), the photoreceptors and, surprisingly, in the cells of the inner nuclear layer as well as in ganglion cells. Most importantly, in dogs, gene transfer also occurred distal to the injection site in neurons of the lateral geniculate nucleus of the brain. Because green fluorescent protein (GFP) was detected along the visual pathway within the brain, we analyzed total DNA extracted from various brain slices using PCR. Vector sequences were detected in many parts of the brain, but chiefly in the contralateral hemisphere.

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