# Nature article: Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents January 08, 2018 Co-authored by current and former Bertarelli-funded PIs Jeffrey Holt and Zheng-Yi Chen [Xue Gao, ](https://www.nature.com/articles/nature25164#auth-1)[Yong Tao, ](https://www.nature.com/articles/nature25164#auth-2)[Veronica Lamas, ](https://www.nature.com/articles/nature25164#auth-3)[Mingqian Huang, ](https://www.nature.com/articles/nature25164#auth-4)[Wei-Hsi Yeh, ](https://www.nature.com/articles/nature25164#auth-5)[Bifeng Pan, ](https://www.nature.com/articles/nature25164#auth-6)[Yu-Juan Hu, ](https://www.nature.com/articles/nature25164#auth-7)[Johnny H. Hu, ](https://www.nature.com/articles/nature25164#auth-8)[David B. Thompson, ](https://www.nature.com/articles/nature25164#auth-9)[Yilai Shu, ](https://www.nature.com/articles/nature25164#auth-10)[Yamin Li, ](https://www.nature.com/articles/nature25164#auth-11)[Hongyang Wang, ](https://www.nature.com/articles/nature25164#auth-12)[Shiming Yang](https://www.nature.com/articles/nature25164#auth-13), [Qiaobing Xu, ](https://www.nature.com/articles/nature25164#auth-14)[Daniel B. Polley, ](https://www.nature.com/articles/nature25164#auth-15)[M. Charles Liberman, ](https://www.nature.com/articles/nature25164#auth-16)[Wei-Jia Kong, ](https://www.nature.com/articles/nature25164#auth-17)[Jeffrey R. Holt, ](https://www.nature.com/articles/nature25164#auth-18)[Zheng-Yi Chen & ](https://www.nature.com/articles/nature25164#auth-19)[David R. Liu](https://www.nature.com/articles/nature25164#auth-20) Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited[1](https://www.nature.com/articles/nature25164#ref1),[2](https://www.nature.com/articles/nature25164#ref2),[3](https://www.nature.com/articles/nature25164#ref3),[4](https://www.nature.com/articles/nature25164#ref4),[5](https://www.nature.com/articles/nature25164#ref5). 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 *Tmc1**Bth* allele differs from the wild-type allele at only a single base pair. Injection of Cas9–guide RNA–lipid complexes targeting the *Tmc1**Bth* allele into the cochlea of neonatal *Tmc1**Bth*/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected *Tmc1**Bth*/+ mice. These findings suggest that protein–RNA complex delivery of target gene-disrupting agents *in vivo* is a potential strategy for the treatment of some types of autosomal-dominant hearing loss. Share on:- [ Facebook ](#) - [ Twitter ](#) - [ Linkedin ](#)