Zhang Yuxin, Wang Shanshan, Xu Miao, Pang Jijing, Yuan Zhilan, Zhao Chen
Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China;Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA.
J Biomed Res. 2019 Aug 30;34(2):114-121. doi: 10.7555/JBR.33.20190056.
Complete congenital achromatopsia is a devastating hereditary visual disorder. Mutations in the gene account for more than 50% of all known cases of achromatopsia. This work investigated the efficiency of subretinal (SR) delivered AAV8 (Y447, 733F) vector containing a human PR2.1 promoter and a human CNGB3 cDNA in / mice. The / mouse was a cone-dominant model with Cngb3 channel deficiency, which partially mimicked the all-cone foveal structure of human achromatopsia with mutations. Following SR delivery of the vector, AAV-mediated CNGB3 expression restored cone function which was assessed by the restoration of the cone-mediated electroretinogram (ERG) and immunohistochemistry. This therapeutic rescue resulted in long-term improvement of retinal function with the restoration of cone ERG amplitude. This study demonstrated an AAV-mediated gene therapy in a cone-dominant mouse model using a human gene construct and provided the potential to be utilized in clinical trials.
完全性先天性全色盲是一种严重的遗传性视觉障碍。该基因的突变占所有已知全色盲病例的50%以上。这项研究调查了在 / 小鼠中，经视网膜下（SR）递送含有人类PR2.1启动子和人类CNGB3 cDNA的AAV8（Y447, 733F）载体的效率。 / 小鼠是一种以视锥细胞为主导的模型，存在Cngb3通道缺陷，部分模拟了具有 突变的人类全色盲的全视锥中央凹结构。在载体经视网膜下递送后，AAV介导的CNGB3表达恢复了视锥细胞功能，这通过视锥细胞介导的视网膜电图（ERG）和免疫组织化学的恢复来评估。这种治疗性挽救导致视网膜功能长期改善，视锥细胞ERG振幅恢复。这项研究在以视锥细胞为主导的小鼠模型中使用人类基因构建体证明了AAV介导的基因治疗，并为在临床试验中应用提供了潜力。
