When David Liu first heard about a strain of mouse from his colleague Zheng-Yi Chen, he got excited. The mice carry a gene, TMC1, with a mutation that leads to deafness over time, giving them the name Beethoven mice. Their mutation matches one in humans that produces the same effect. The mutation is dominant; if it is present, hearing loss is certain.
Liu, a chemical biologist at the Broad Institute, works with the noted CRISPR-Cas9 technology, which targets and changes precise stretches of DNA. In the Beethoven mouse, he saw an ideal testing ground for the new gene editing technology, bringing hope that it might accomplish something new: improve hearing by disrupting a single genetic mutation. Other forms of gene modification add copies of genes, but are ineffectual if a dominant mutation remains.
In a paper published Dec. 20 in Nature, Liu, who is also a professor at Harvard University and an investigator of the Howard Hughes Medical Institute, and Chen, a hearing biologist at Massachusetts Eye and Ear Infirmary and professor of otolaryngology at Harvard, along with colleagues, report that the idea worked. The mice treated showed improved hair cell survival and hearing thresholds, and were startled by loud noises while untreated mice weren’t. “To our knowledge, this is the first time that genome editing has been used to correct hearing loss in an animal model of human genetic deafness,” Liu says. “There is a lot of work to do to translate these results into patients, but there is some proof of principle here.”
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