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
INSERM U649, CHU Hotel-Dieu, Nantes, France.
Mol Ther. 2008 May;16(5):916-23. doi: 10.1038/mt.2008.41. Epub 2008 Mar 11.
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.
重组腺相关病毒（rAAV）载体是向视网膜进行基因转移的最有效的基因递送载体之一。本研究评估了rAAV8血清型载体在大鼠和犬眼内递送方面的行为。视网膜下递送AAV2/8.gfp载体可在视网膜色素上皮（RPE）、光感受器中实现高效基因转移，令人惊讶的是，在内核层细胞以及神经节细胞中也能实现高效基因转移。最重要的是，在犬中，基因转移也发生在大脑外侧膝状体神经元注射部位的远端。由于在大脑内的视觉通路中检测到了绿色荧光蛋白（GFP），我们使用聚合酶链反应（PCR）分析了从各种脑切片中提取的总DNA。在大脑的许多部位都检测到了载体序列，但主要在对侧半球。
