Xue Gao, Yong Tao, Veronica Lamas, Mingqian Huang, Wei-Hsi Yeh, Bifeng Pan, Yu-Juan Hu, Johnny H Hu, David B Thompson, Yilai Shu, Yamin Li, Hongyang Wang, Shiming Yang, Qiaobing Xu, Daniel B Polley, M Charles Liberman, Wei-Jia Kong, Jeffrey R Holt, Zheng-Yi Chen, David R Liu
Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair...
January 11, 2018: Nature