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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2016-12-06T00:00:00-05:00" class="date-display-single">December 6, 2016</span></p><div class='syndicate'><h1>Novel gene-editing method improves vision in blind rats </h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.</li>
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<li>The method enabled replacement of a faulty gene in neurons and partially restored vision in blind rats. The technique thus holds promise as a potential tool for gene therapy. </li>
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<picture title="Neurons in adult mouse brain">
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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/2016/20161206-gene-editing.jpg?itok=K-_vN9Ba&timestamp=1481039263 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/2016/20161206-gene-editing.jpg?itok=MwlC5ApQ&timestamp=1481039263 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/2016/20161206-gene-editing.jpg?itok=v48__9WS&timestamp=1481039263 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/2016/20161206-gene-editing.jpg?itok=YBY37ttg&timestamp=1481039263 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/2016/20161206-gene-editing.jpg?itok=36MqRGC8&timestamp=1481039263 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/2016/20161206-gene-editing.jpg?itok=MwlC5ApQ&timestamp=1481039263" alt="Neurons in adult mouse brain" title="Neurons in adult mouse brain" />
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</picture><span class="caption">The green-colored cells are neurons in a mouse brain that were successfully modified using the new gene-editing technique.</span><span class="credit">Izpisua Belmonte Lab, Salk Institute</span></div>
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</div><p>Gene-editing techniques like CRISPR/Cas9 can successfully replace faulty genes, and scientists have been exploring their therapeutic potential. But insertion of new genes has generally been limited to dividing cells, like those in the skin and gut, because the techniques depend on processes that are only active during cell division. Most of the body’s cells, however, are non-dividing, including those in the eye, brain, and heart.</p>
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<p>To address this limitation, a group of researchers led by Dr. Juan Carlos Izpisua Belmonte at the Salk Institute for Biological Studies in San Diego set out to develop a more versatile approach. Their goal was to develop a technique that could insert new genes even into cells that weren’t dividing. The research was funded in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). Results were published in <em>Nature</em> on December 1, 2016.</p>
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||
<p>The researchers focused on a DNA-repair mechanism called NHEJ (non-homologous end-joining). NHEJ repairs DNA breaks by rejoining broken DNA ends. It’s active in both dividing and non-dividing cells. This makes it a useful partner to the CRISPR/Cas9 gene-editing tool, which can snip out DNA pieces at precise locations.</p>
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||
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||
<p>The scientists tailored the NHEJ machinery for use along with CRISPR/Cas9. They named the new approach HITI (homology-independent targeted integration). With HITI, a gene is targeted using CRISPR/Cas9 and replaced by a new gene using the cell’s routine NHEJ repair mechanism.</p>
|
||
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||
<p>To test the approach in non-dividing cells, the researchers used a harmless virus to deliver the specialized HITI package into a sample of neurons. This led to site-specific insertion of the new gene into these neurons. The team next tested the HITI-enabled gene insertion method in non-dividing cells in mice. They were able to incorporate the new gene into the brain, muscle, kidney, heart, and liver of adult mice.</p>
|
||
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||
<p>The scientists next explored whether HITI might be used as a gene-replacement tool to treat disease. They tested a rat model of retinitis pigmentosa, an inherited eye disorder that causes retinal degeneration and eventual blindness in humans.</p>
|
||
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||
<p>The team used HITI to replace the mutated <em>Mertk</em> gene that causes blindness in these rats with a functional copy of the gene. The functional gene became incorporated into the rat genome. After 4 weeks, MERTK protein expression was observed in the retina. Light-sensitive eye tests showed improved responses, indicating a partial rescue of vision.</p>
|
||
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<p>Although the researchers chose to use the CRISPR/Cas9 tool along with HITI in this study, other gene-editing techniques could also be coupled with HITI to insert new genes into the genome.</p>
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||
<p>“We now have a technology that allows us to modify the DNA of non-dividing cells, to fix broken genes in the brain, heart, and liver,” Izpisua Belmonte says. “It allows us, for the first time, to be able to dream of curing diseases that we couldn’t before, which is exciting.”</p>
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||
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||
<p>With the eventual goal of developing HITI for use in the clinic, the researchers are working to improve the efficiency of the technique.</p>
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<p>―by Anita Ramanathan </p>
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</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/gene-editing-corrects-sickle-cell-mutation" target="_top">Gene Editing Corrects Sickle Cell Mutation</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/gene-editing-improves-muscle-mice-muscular-dystrophy" target="_top">Gene Editing Improves Muscle in Mice with Muscular Dystrophy</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/method-can-target-specific-microbes" target="_top">Method Can Target Specific Microbes</a></li><li><a href="https://www.cancer.gov/about-cancer/causes-prevention/research/crispr" target="_top">CRISPR: Genome Editing Comes of Age</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/27851729">In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration.</a> Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J, Kim EJ, Hatanaka F, Yamamoto M, Araoka T, Li Z, Kurita M, Hishida T, Li M, Aizawa E, Guo S, Chen S, Goebl A, Soligalla RD, Qu J, Jiang T, Fu X, Jafari M, Esteban CR, Berggren WT, Lajara J, Nuñez-Delicado E, Guillen P, Campistol JM, Matsuzaki F, Liu GH, Magistretti P, Zhang K, Callaway EM, Zhang K, Belmonte JC. <em>Nature.</em> 2016 Dec 1;540(7631):144-149. doi: 10.1038/nature20565. Epub 2016 Nov 16. PMID: 27851729.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Heart, Lung, and Blood Institute (NHLBI), National Institute of Neurological Disorders and Stroke (NINDS), National Eye Institute (NEI), and National Cancer Institute (NCI); Leona M. and Harry B. Helmsley Charitable Trust; G. Harold and Leila Y. Mathers Charitable Foundation; McKnight Foundation; Moxie Foundation; Fundacion Dr. Pedro Guillen; and Universidad Católica San Antonio de Murcia.</p>
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