Template-independent genome editing in the Pcdh15 mouse, a model of human DFNB23 nonsyndromic deafness
Lian Liu, Linzhi Zou, Kuan Li, Hanqing Hou, Qun Hu, Shuang Liu, Jie Li, Chenmeng Song, Jiaofeng Chen, Shufeng Wang, Yangzhen Wang, Changri Li, Haibo Du, Jun-Liszt Li, Fangyi Chen, Zhigang Xu, Wenzhi Sun, Qianwen Sun, Wei Xiong
Abstract
mice, an animal model of human nonsyndromic deafness DFNB23. Identified by an ex vivo evaluation system in cultured cochlear explants, the selected guide RNA restores reading frame in approximately 50% of indel products and recovers mechanotransduction in more than 70% of targeted hair cells. In vivo treatment shows that half of the animals gain improvements in auditory responses, and balance function is restored in the majority of injected mutant mice. These results demonstrate that NHEJ-mediated reading-frame restoration is a simple and efficient strategy in postmitotic systems.