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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2024-07-30T00:00:00-04:00" class="date-display-single">July 30, 2024</span></p><div class='syndicate'><h1>Genome editing restores hearing in mice</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Scientists developed a genome editing method to restore hearing in adult mice with a rare type of genetic hearing loss. </li>
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<li>With additional study, this type of approach might one day help to reverse some types of inherited hearing loss in people.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Scanning electron micrograph images of mouse inner ear hair cells.">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2024/20240730-hair-cells.jpg?itok=BQZgol6H&timestamp=1722346346 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20240730-hair-cells.jpg?itok=CSrR03rR&timestamp=1722346346 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2024/20240730-hair-cells.jpg?itok=CRK-xIGL&timestamp=1722346346 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2024/20240730-hair-cells.jpg?itok=4kwh6wiC&timestamp=1722346346 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2024/20240730-hair-cells.jpg?itok=IQG8bUqZ&timestamp=1722346346 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20240730-hair-cells.jpg?itok=CSrR03rR&timestamp=1722346346" alt="Scanning electron micrograph images show straight rows of hair-like structures in treated ears and disorganized ones in untreated ears." title="Scanning electron micrograph images of mouse inner ear hair cells." />
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</picture><span class="caption">Electron micrograph images of treated (left) and untreated (right) inner ear hair cell bundles. The asterisks mark the structural damage in the untreated ear. </span><span class="credit">Science Translational Medicine</span></div>
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</div><p>For over half of children born with hearing loss, a single genetic abnormality is to blame. This is called inherited deafness, or genetic deafness. Hearing loss can impair a child’s speech, language, and social skills. Early interventions can often help. But no medications or other treatments have yet been approved for slowing or reversing progression of inherited deafness.</p>
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<p>Scientists have been searching for ways to restore hearing via gene editing, which entails modifying the genetic sequence. Some have successfully improved hearing in mice with different types of hearing loss. But to date, such studies had only been successful in newborn mice, which still have immature structures in their inner ear. These structures continue to change in shape and function until adulthood. In contrast, the inner ear is fully developed in newborn humans.</p>
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||
<p>A research team led by Dr. Zheng-Yi Chen at Mass Eye and Ear in Boston reasoned that developing a gene editing approach that works in adult mice, with a fully mature inner ear, might make it more likely to also work in humans. Their study appeared on July 10, 2024, in <em>Science Translational Medicine</em><em>.</em></p>
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||
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||
<p>The scientists created a mouse model with a specific mutation in the <em>microRNA-96</em> (<em>MIR96)</em> gene. MIR96 helps to regulate gene activity in the ear’s tiny hair cells, which transform sound into electrical signals. Mice with the mutation lose their hair cells and develop complete hearing loss in the high frequencies four weeks after birth. In humans, the same mutation causes a rare type of genetic hearing loss called autosomal dominant deafness-50 (DFNA50). People born with DFNA50 tend to have progressive hearing loss beginning in their teens.</p>
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<p>The research team developed a CRISPR-Cas9 gene editing system that could disable faulty versions of the <em>MIR96 </em>gene in living mice. A harmless adeno-associated virus (AAV) was used to deliver the system into cells. This was injected into the inner ear of some mutant mice at 3 weeks of age, before the onset of hearing loss. Other mice received the injection at 6 weeks, as adults with hearing loss. Each mouse received the injection in only one ear, with the other ear serving as a control.<em> </em></p>
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<p>The treatment led to better survival of hair cells and improved long-term hearing in the treated ear of both sets of mice. The earlier intervention led to greater improvements. In contrast, untreated ears developed hearing loss as expected.</p>
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||
<p>The scientists also found evidence that the intervention was safe. AAV didn’t integrate into the genome of the cells it infected, which could lead to unexpected and harmful outcomes. The researchers note that additional preclinical studies will be needed in different animal models before this type of approach could be tested in humans.</p>
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<p>“We restored the animals’ hearing, and this was sustained for at least nine months,” Chen says. “Now, we have these results that show new possibilities for genome editing. These advances are bringing in a new era of treatments for people who have genetic deafness.”</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/researchers-create-developmental-map-mouse-cochlea" target="_top">Researchers Create Developmental Map of Mouse Cochlea </a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/technique-treats-hereditary-deafness-mice" target="_top">Technique Treats Hereditary Deafness in Mice </a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/blueprint-cell-development-inner-ear" target="_top">A Blueprint of Cell Development in the Inner Ear </a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/hearing-different-frequencies" target="_top">Hearing Different Frequencies </a></li><li><a href="https://newsinhealth.nih.gov/2018/05/struggling-hear" target="_top">Struggling to Hear? Tiny Devices Can Keep You Connected</a></li><li><a href="https://www.nidcd.nih.gov/health/hearing-ear-infections-deafness" target="_top">Hearing, Ear Infections, and Deafness</a></li><li><a href="https://www.nidcd.nih.gov/health/how-do-we-hear" target="_top">How Do We Hear?</a></li><li><a href="https://www.genome.gov/about-genomics/policy-issues/what-is-Genome-Editing" target="_top">What Is Genome Editing?</a></li><li><a href="https://www.cdc.gov/hearing-loss-children-guide/parents-guide-genetics/index.html" target="_top">A Parent’s Guide to Genetics and Hearing Loss (CDC)</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/38985856/">Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation.</a> Zhu W, Du W, Rameshbabu AP, Armstrong AM, Silver S, Kim Y, Wei W, Shu Y, Liu X, Lewis MA, Steel KP, Chen ZY. <em>Sci Transl Med.</em> 2024 Jul 10;16(755):eadn0689. doi: 10.1126/scitranslmed.adn0689. Epub 2024 Jul 10. PMID: 38985856.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s Common Fund Somatic Cell Genome Editing program, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Deafness and other Communications Disorders (NIDCD), and National Human Genome Research Institute (NHGRI).</p>
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NIH Research Matters<br />
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Bldg. 31, Rm. 5B52, MSC 2094<br />
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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