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This gene therapy stopped mice from going deaf — and could save some humans’ hearing too

This gene therapy stopped mice from going deaf — and could save some humans’ hearing too


‘We have entered the age where the human genome is a real drug target.’

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Illustration: James Bareham / The Verge

Scientists have successfully tweaked the DNA of mice with a specific genetic mutation to prevent them from going completely deaf. If the gene-editing technique is proven safe, it could one day be used to treat the same type of hearing loss in people.

Researchers injected the gene-editing tool CRISPR-Cas9 inside the ears of live mice with a deafness-causing genetic mutation. The molecular scissors were able to precisely cut the disease-causing copy of the gene without disrupting the healthy copy, according to a study published today in Nature. Even though the researchers think they were able to repair only a small fraction of cells in the ear, that prevented treated mice from losing all their hearing.

“the human genome is a real drug target.”

Gene editing has been making huge strides in the past few years. Just last month, scientists attempted to edit a person’s DNA inside his own body for the first time in order to cure a debilitating genetic disorder called Hunter syndrome. The technique described in today’s study also attempts to edit DNA inside the body of a living animal — in this case, mice. Though the treatment is still years from coming to a clinic near you, it’s an important step in the development of gene therapies, which tinker with genes in order to treat or prevent diseases.

“We have entered the age where the human genome is a real drug target,” says Fyodor Urnov, the associate director at Altius Institute for Biomedical Sciences, who was not involved in the study. The researchers “have provided the first important step and a strong perspective of hope for people who have this mutation.”

The gene-editing tool CRISPR-Cas9 is based on a defense mechanism bacteria use to ward off viruses by cutting off bits of their DNA. Scientists have engineered that mechanism to edit pieces of the genetic code, creating unusually muscular beagles, for instance, and mosquitoes that don’t transmit malaria. The technique is advancing fast: Last year in China, doctors took immune cells from a patient with lung cancer, edited them, and then injected the cells back into the patient to help defeat the disease. Earlier this year, scientists in the US used CRISPR to edit human embryos and try to correct a gene mutation that causes a dangerous heart condition.

The latest tool, developed by researchers in the US and China, targets the ear to treat a rare form of genetic deafness. Although people can lose their hearing for a variety of reasons — old age, as well as exposure to loud noises — genetics are behind a little less than half of all deafness cases, says study co-author David Liu, a professor of chemistry and chemical biology at Harvard, who also has affiliations with the Broad Institute and the Howard Hughes Medical Institute. The hearing-loss disease tackled in this study is caused by mutations in a gene called TMC1. These mutations cause the death of so-called hair cells in the inner ear, which convert mechanical vibrations like sound waves into nerve signals that the brain interprets as hearing. As a result, people start losing their hearing in their childhood or in the 20s, and can go completely deaf by their 50s and 60s.

CRISPR-Cas9 mixed with a lipid droplet

To snip those mutant copies of the gene, Liu and his colleagues mixed CRISPR-Cas9 with a lipid droplet that allows the gene-editing tool to enter the hair cells and get to work. When the concoction was injected into one ear of newborn mice with the disease, the molecular scissors were able to precisely cut the deafness-causing copy of the gene while leaving the healthy copy alone, even if the two copies differ by just one base pair. The treatment allowed the hair cells to stay healthier and prevented the mice from going deaf.

After four weeks, the untreated ears could only pick up noises that were 80 decibels or louder, roughly as loud as a garbage disposal, Liu says. Instead, the injected ears could typically hear sounds in the 60 to 65 decibel range, which is the same as a quiet conversation. “If one can translate that 15 decibel improvement in hearing sensitivity in humans, it would actually make a potential difference in the quality of their hearing capability,” Liu tells The Verge.

After eight weeks, the researchers performed a startle test — “the equivalent of walking up behind your friend and yelling ‘Boo!’ and watching them jump,” Liu says. When the untreated mice were put in a soundproof chamber and exposed to a pulse of loud noise, they didn’t jump — they were completely deaf. But the loud sound startled the mice who received the gene therapy even in only one ear. “They have proven that when you get rid of just the mutant copy, you prevent hearing loss,” Urnov says. “The cell can, in fact, not just live but thrive when you get rid of the mutant copy.”

“That is really remarkable, that this is happening in our lifetime.”

The scientists don’t know exactly how many hair cells they were able to repair. They think it was only a fraction — possibly 10 to 25 percent. But they do know that their technique was very precise, disrupting 20 mutant copies of the gene for every healthy copy of the gene. “The shortcoming is the efficiency wasn’t super high, but the good news is, it turns out they didn’t need it,” Urnov says. In the future, the technique could help develop treatments for other types of genetic deafness, and even other genetic diseases as well, Liu says.

Before the treatment can be used in people, however, it needs to be tested on human cells and then on larger animals like pigs or primates. Making sure that the therapy is effective and safe could take about a decade, Liu says, but Urnov is more optimistic: two years. Clinical trials to edit people’s DNA to cure genetic disorders are already taking place, although with a different gene-editing tool called zinc fingers, Urnov says. So there’s a clear path ahead for how the treatment can get approved for use in people, he says.

“We’re entering a time when we can genetically manipulate organs in vivo rather than manipulate cells in a dish and then transplant them,” Urnov says. “That is really remarkable, that this is happening in our lifetime.”