Gene editing could one day help people at risk of losing their hearing due to genetic mutations, according to new research.
Xue (Sherry) Gao, an assistant professor of chemical and biomolecular engineering at Rice University, is co-lead author of a new paper in Nature that reports on the promise of gene editing to treat autosomal dominant hearing diseases.
Gao performed the research while a postdoctoral associate under the guidance of David Liu at Harvard University. She says that while hearing diseases are typically not life-threatening, hearing loss is the most common human sensory impairment and has a substantial impact on individuals and society.
Many genetic mutations affect the sensory hair cells that amplify acoustic vibrations and translate them into electrical nerve signals. Gao says humans are born with about 12,000 hair cells that do not regenerate spontaneously if damaged. It has been reported that one in every 1,000 infants born in the United States has genetic mutations that contribute to deafness. Nevertheless, she says, few treatments are available to slow or reverse genetic deafness.
The researchers used rodent models of human genetic disease since a rodent cochlea—the organ in the inner ear that sends sounds to the brain—is strikingly similar to that of humans, Gao says. They focused on editing hair cells inside the cochlea, which they found suitable for the delivery of one-time, nonreplicable edits through Cas9/single-guide RNA. The RNA is a ribonucleotide (RNP) protein complex designed to specifically disrupt genes associated with hearing loss.
“Delivering the RNP complex instead of DNA into the cochleae showed significantly fewer off-target effects,” Gao says. This enabled the researchers to effectively disrupt one genomic site containing a single point mutation and avoid the billions of other sites available for modification.
Eight weeks after injecting the protein complex into the cochleae of rodents with progressive, genetic hearing loss, the researchers observed higher hair cell survival rates compared with those in a control group that did not receive the injection.
Tests that measured brain waves in response to audio cues showed the treatment significantly preserves the animals’ hearing compared with the control group. The treatment also helped preserve the injected animals’ acoustic behavioral reflexes, according to the researchers.
“We hope to develop more advanced genome-editing tools and test them on other animal species to demonstrate their safety and effectiveness as we move them toward humans,” says Gao, whose lab is at Rice’s BioScience Research Collaborative.
Gao’s primary collaborators on the paper were co-lead author Yong Tao and Zheng-Yi Chen of the Massachusetts Eye and Ear Infirmary. The Defense Advanced Research Projects Agency and the National Institutes of Health supported the research.