Development of a gene therapy for inherited corneal disease using a lentivirus vector

我们研究了一种基因治疗遗传性角膜疾病，所谓的角膜营养不良，使用慢病毒载体。慢病毒载体可以在体内外感染非分裂细胞，并介导转基因在各种组织中的有效转移和持续长期表达。在这个项目中，我们获得了以下结果。(1)我们已经开发了一种增强子-启动子区域，其驱动感兴趣的基因的角膜特异性表达。(2)我们使用CHST 6基因的靶向破坏创建了黄斑角膜营养不良的敲除小鼠。(3)我们已经开发了一种用慢病毒载体转导的角膜上皮片移植方法。(4)我们已经证明，慢病毒载体可以体外培养角膜内皮细胞。结果表明，用慢病毒载体进行离体基因治疗治疗角膜营养不良具有良好的临床应用前景。

We investigated a gene therapy for inherited corneal diseases, so-called corneal dystrophies, using a lentivirus vector. Lentivirus vector can transduce non-dividing cells in vitro and in vivo, and mediate efficient transfer and sustained long-term expression of the transgene in varieties of tissues. In this project, we obtained the following results.(1) We have developed an enhancer-promotor region that drives a cornea-specific expression of a gene of interest.(2) We have created knockout mice of macular corneal dystrophy using a targeted destruction of CHST6 gene.(3) We have developed a transplantation approach of corneal epithelial sheets transduced with a lentivirus vector.(4) We have shown that lentivirus vector can transduce ex vivo corneal endothelial cells. The results suggest promising clinical capabilities for ex vivo gene therapy for the treatment for corneal dystrophies with a lentivirus vector.