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

我们使用慢病毒载体研究了一种遗传性角膜疾病的基因疗法，即所谓的角膜营养不良。慢病毒载体可以在体外和体内转导未分裂细胞，并介导转基因基因在多种组织中的高效转移和持续长期表达。在本项目中，我们获得了以下结果：(1)我们开发了一个增强子-启动子区域来驱动目的基因的角膜特异性表达。(2)我们通过靶向破坏CHST6基因建立了黄斑性角膜营养不良基因敲除小鼠。(3)我们发展了一种慢病毒载体转导的角膜上皮片移植方法。(4)我们已经证明了慢病毒载体可以转导体外角膜内皮细胞。这些结果表明，慢病毒载体用于治疗角膜营养不良的体外基因治疗具有很好的临床应用前景。

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.