Xue Gao, Harvard University, Cambridge, USA, and colleagues have, for the first time, corrected a dominantly inherited form of genetic deafness with CRISPR/Cas9. In experiments with mice, the tool successfully switched off the defective copy of a gene leading to progressive hearing loss and deafness. A single wrong letter in just one copy of a gene called TCM1 can lead to progressive hearing loss or even deafness in humans. The scientists injected CRISPR/Cas9 directly into the fine hair cells in the inner ear of newborn mice. The animals were diseased with the defect in the TCM1 gene.
While untreated mice no longer responded to noises below 80 decibels after four weeks, the treated animals still showed reactions up to a volume of 65 decibels. Even after eight weeks, these animals were scared when it suddenly became very loud. The control group did not respond to such sounds at this time.
In 94 % of the treated cells, the CRISPR/Cas9 tool had been placed in the right place in the genome and only in 6% an intact rather than the defective copy of the gene was damaged. This high success rate also had to do with how the researchers brought the gene-shears to their site of action – namely directly and as a fully assembled molecular complex. When CRISPR/Cas9 was introduced in the form of individual DNA elements, which the cells themselves then use to produce the gene scissors, the accuracy and thus the safety of the treatment dropped.
According to the researchers, their 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.
- Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents,
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,
Nature 2017.
https://doi.org/10.1038/nature25164
