Massachusetts Eye and Ear/Harvard Medical School associate professor Zheng-Yi Chen, D.Phil. (1995 ERG), and colleagues delivered a CRISPR/Cas9 genome editing complex directly into the inner ear hair cells of mice, preventing hearing loss in an animal model of genetic progressive deafness. The CRISPR/Cas9 therapy disabled a mutated form of the gene Tmc1, the first time that a gene editing protein has been ferried directly into the relevant cells to halt progression of genetic hearing loss.

A single-letter mutation in the gene Tmc1 and carrying only one of two copies of the mutated gene both lead to progressive hearing loss in mice and humans. With the mutated gene disabled, the inner ear hair cells survive, and mice otherwise genetically destined to become deaf retained a portion of their hearing. In a report published in Nature in December 2017, the team says that at four weeks, untreated mice were unresponsive to sound below an average of 80 decibels, while treated mice responded to sound at approximately 65 decibels. At eight weeks, treated mice also retained their instinctive physical “startle” response to sudden loud sound, while the untreated mice did not respond. The researchers said delivering the Cas9 protein itself locally, instead of DNA elements that the cell can use to build Cas9, improved the DNA specificity and potential safety of the treatment. —Massachusetts Eye and Ear