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  • Rewriting Life

    The Easiest Place to Use CRISPR Might Be in Your Ear

    Scientists are hopeful they can inject the gene-editing technology directly into the ear to stop hereditary deafness.

    We all know that CRISPR is the next big thing in gene-editing treatments. But how do you get the versatile genetic scissors into a person’s body?

    The usual way might be to load the gene-editing instructions into billions of viruses and use those to infect a person’s cells. But some scientists are experimenting with delivery tricks that could make treatments easier to pull off (see "Five Ways to Get CRISPR into the Body"). One of them is Zhen-Yi Chen, a hearing researcher in Boston who has been treating mice by directly injecting the gene-editing components into their ears.

    It’s not quite as simple as CRISPR ear drops, but it’s pretty close.

    The experiments in Chen’s lab at the Massachusetts Eye & Ear Infirmary involve mice who share a genetic defect that humans have that causes gradual hearing loss. One breed is called “Beethoven,” after the composer who eventually couldn’t hear his own music.

     “They saw a beautiful rescue of hearing,” says Xue Zhong Liu, an ear doctor who directs the center for hereditary disease at the University of Miami, who learned of the results at a meeting this year. “It will be the first example to show how CRISPR is used for progressive hearing loss."

    Actually, doctors aren’t clear on what physiological changes to ear cells these genetic errors actually cause. The inner ear is enclosed in the hardest bone in the body, says Liu, and doctors don’t often get to peek inside.

    But knowing what genes are to blame may be enough. Chen says he’d been trying some more complex approaches to treat hearing when it dawned on him. “With CRISPR we can just do direct delivery, one shot delivery, and the correction is permanent,” says Chen. 

    Learn more about how CRISPR works.

    He and David Liu, a gene-editing specialist at Harvard University, have found ways to package the CRISPR cutting protein into fatty blobs called liposomes. These are injected into a mouse’s inner ear, home to delicate hair cells that sense vibrations and send messages to the brain. The target is a gene called TMC1. CRISPR’s job: put it out of commission with a quick snip to its DNA letters.

    The animal’s hearing is tested by putting it to sleep inside a soundproof metal chamber, where it’s exposed to various noises. An electrode attached to its brain stem reads out whether the message got through.

    In the best cases, Chen and Liu have reported, mice treated with CRISPR retain significant hearing at two months of age. Otherwise, they’d be so deaf they couldn’t hear an 80 decibel noise—about what a food blender makes.

    Each of your ears has, deep inside it, about 16,000 cells that sprout sensory hairs. That is how sound is picked up. You can damage those cells by standing in front of the speakers at a rock show. Some genetic conditions have the same result. 

    Chen works on so-called dominant genetic disorders, meaning just one parent needs to pass on an aberrant gene for the problem to arise. It causes the sort of hearing loss that develops gradually, over the years, starting before the age of 25 and leaving people profoundly deaf by 50.

    Chen’s next steps will take place in China, where scientists are enthusiastically pursuing gene-editing technology. He’s working with a team there to create pigs that are genetically modified to have the same gene mutations as people do. “The pig will absolutely go deaf,” says Chen, given how similar their ears are to ours.

    If the CRISPR injections can prevent that, Chen says, “we can move the endeavors into humans.” That’s another advantage of working in China. Hospitals there, he says, have already registered thousands of people with the genetic disorder, whereas in the U.S., very few affected families are being tracked. “It’s on a totally different scale,” says Chen. “That’s why we will do it there first.”

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