Scientists have now edited genes inside mice to prevent a form of inherited deafness.
While cautioning that much more research is needed, the scientists said they hope the technique might someday be used to prevent deafness in children born in families with a history of genetic hearing loss.
Before that could happen, however, extensive tests would be needed to determine whether the treatment is safe — and whether it would actually work in humans.
"We're hopeful that our results will help guide the development of such strategies," says David Liu, a genetic engineer at Broad Institute, the Massachusetts Institute of Technology and Harvard University. The results were reported Wednesday in the journal Nature.
Liu performed his experiments on a type of mouse known as a Beethoven mouse. These mice carry a defect that causes them to lose their hearing starting early in life. It's probably not what caused the famous German composer Ludwig von Beethoven's deafness. Still, the same defect does cause deafness in some families.
"Humans that are born with even one bad copy of this gene experience progressive hearing loss that's evident in their early childhood and by the time they reach late childhood they're profoundly deaf," Liu says.
Liu used the gene-editing technique CRISPR Cas-9 to design a way to knock out the defective gene, which destroys tiny hairs inside the ear needed for normal hearing. Liu then injected the gene-editor into the ears of Beethoven mice one day after the animals were born.
Once inside the ear, the gene editor "homes in on the mutant gene" and cuts the DNA "so that mutant gene can no longer poison the hair cells and cause the hair cells to eventually die," Liu says.
Since these mice still have a second, healthy version of the necessary gene, the idea was that the elimination of the defective gene would allow healthy hearing development.
When Liu tested the treated mice a month later, they could hear much better in the ears that got edited.
The treated ears could hear sounds that were "about as quiet as a normal quiet conversation," Liu says, "whereas the uninjected ears of the same mice have lost enough of their hearing that they required sounds that were about as loud as a garbage disposal in order to register a response."
Similar approaches could possibly be developed to prevent hearing loss in babies born with the same defect and other inherited mutations that cause hearing loss, Liu says. In addition, gene editing could potentially restore hearing to people who lost it from loud noise or infections, he says.
The latest work follows experiments published in 2015 using a different gene-editing technique to alter the same inherited form of deafness in mice.
Other researchers praised the recent work by Liu and his colleagues.
"It is is an extraordinary thrill to be working in this field at this time," says Fyodor Urnov, associate director at the Altius Institute for Biomedical Sciences in Seattle. Urnov wrote a commentary accompanying the report in the journal. "We no longer are relegated to just sequencing DNA and staring glumly at genetic destiny."
The development is the latest in the rapidly moving field of gene therapy and gene editing. The Food and Drug Administration approved the first gene-therapy product to treat a form of leukemia in August and a second for a form of lymphoma in October. On Tuesday, the agency approved the first gene therapy to treat an inherited disorder — a form of inherited blindness.
ARI SHAPIRO, HOST:
Scientists have used a new genetic engineering technique to prevent deafness in mice. The hope is that someday it could help doctors do the same thing for people. As NPR health correspondent Rob Stein reports, this is the latest development in the rapidly growing field of gene therapy.
ROB STEIN, BYLINE: We all know one of the most famous people to lose one of their most important senses.
(SOUNDBITE OF BEETHOVEN'S "SYMPHONY NO. 5")
STEIN: Beethoven, the German composer who gave the world "Symphony No. 5" and so much more glorious music, even as his own symphonies faded to silence in his own ears.
(SOUNDBITE OF BEETHOVEN'S "SYMPHONY NO. 5")
STEIN: So when David Liu decided to use genetic engineering to try to prevent deafness, he started with a mouse named after...
DAVID LIU: Ludwig van Beethoven.
STEIN: Because these Beethoven mice carry a genetic defect that makes them go deaf, too. It's probably not what stole Beethoven's hearing, but the same defect runs in some families.
LIU: Humans that are born with even one bad copy of this gene experience progressive hearing loss that's evident in their early childhood, and by the time they reach sort of late childhood, they are profoundly deaf.
STEIN: Because this mutant gene destroys the tiny sensory hairs inside the ear that let us hear. Liu's a gene-editing expert at Harvard and MIT. So he designed a genetic scalpel to splice out this bad gene and injected it into the ears of these Beethoven mouse pups one day after they were born.
LIU: And then it homes in on the mutant gene. It cuts the DNA so that mutant gene can no longer poison the hair cells and cause the hair cells to eventually die.
STEIN: Giving the mice enough healthy hair cells in their ears to save their hearing. When Liu tested the gene-edited mice a month later, he was thrilled. It worked.
LIU: The ears that were injected with our treatment were hearing sounds that were about as quiet as a normal, quiet conversation, whereas the uninjected ears of the same mice have lost enough of their hearing that they required sounds that were about as loud as a garbage disposal in order to register a response. So it's quite a bit of difference.
STEIN: Now, Liu stresses it will take a lot more research before anyone tries something like this on people. But he hopes the same thing could eventually prevent many kinds of inherited deafness. And that's not all.
LIU: We and others are interested in developing different kinds of genome-editing strategies to actually try to restore hearing by stimulating actual regeneration of hair cells, which has the promise of potentially treating not just genetic forms of hearing loss but maybe even environmental forms as well.
STEIN: Like deafness caused by loud noise or infections. Other researchers say the advance is a big deal. Fyodor Urnov is a genetic engineer at the Altius Institute for Biomedical Sciences in Seattle. He says it shows how gene-editing techniques are revolutionizing medicine.
FYODOR URNOV: It is an extraordinary thrill to be working in this field at this time. We no longer are relegated to just sequencing DNA and staring glumly at genetic destiny.
STEIN: While a lot more research is needed before anyone cures deafness with gene editing, the Food and Drug Administration recently approved the first gene therapies, one for leukemia and another for lymphoma, and OK'd another to reverse a rare form of genetic blindness just yesterday. In the meantime, scientists are testing gene-editing therapies for many other diseases. Rob Stein, NPR News.
(SOUNDBITE OF BEETHOVEN'S "SYMPHONY NO. 5") Transcript provided by NPR, Copyright NPR.