{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:01:29Z","timestamp":1793084489914,"version":"4.5.0"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"654","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,7,20]]},"abstract":"<jats:p>\n            Programmable RNA editing tools enable the reversible correction of mutant transcripts, reducing the potential risk associated with permanent genetic changes associated with the use of DNA editing tools. However, the potential of these RNA tools to treat disease remains unknown. Here, we evaluated RNA correction therapy with Cas13-based RNA base editors in the myosin VI p.C442Y heterozygous mutation (\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>C442Y\/+<\/jats:sup>\n            ) mouse model that recapitulated the phenotypes of human dominant-inherited deafness. We first screened several variants of Cas13-based RNA base editors and guide RNAs (gRNAs) targeting\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>C442Y<\/jats:sup>\n            in cultured cells and found that mini dCas13X.1-based adenosine base editor (mxABE), composed of truncated Cas13X.1 and the RNA editing enzyme adenosine deaminase acting on RNA 2 deaminase domain variant (ADAR2dd\n            <jats:sup>E488Q<\/jats:sup>\n            ), exhibited both high efficiency of A &gt; G conversion and low frequency of off-target edits. Single adeno-associated virus (AAV)\u2013mediated delivery of mxABE in the cochlea corrected the mutated\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>C442Y<\/jats:sup>\n            to\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>WT<\/jats:sup>\n            allele in homozygous\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>C442Y\/C442Y<\/jats:sup>\n            mice and resulted in increased\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>WT<\/jats:sup>\n            allele in the injected cochlea of\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>C442Y\/+<\/jats:sup>\n            mice. The treatment rescued auditory function, including auditory brainstem response and distortion product otoacoustic emission up to 3 months after AAV-mxABE-\n            <jats:italic>Myo6<\/jats:italic>\n            injection in\n            <jats:italic>Myo6<\/jats:italic>\n            <jats:sup>C442Y\/+<\/jats:sup>\n            mice. We also observed increased survival rate of hair cells and decreased degeneration of hair bundle morphology in the treated compared to untreated control ears. These findings provide a proof-of-concept study for RNA editing tools as a therapeutic treatment for various semidominant forms of hearing loss and other diseases.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abn0449","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T17:59:46Z","timestamp":1658339986000},"source":"Crossref","is-referenced-by-count":86,"title":["Rescue of autosomal dominant hearing loss by in vivo delivery of mini dCas13X-derived RNA base editor"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3921-9395","authenticated-orcid":true,"given":"Qingquan","family":"Xiao","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China."},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0106","authenticated-orcid":true,"given":"Zhijiao","family":"Xu","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China."},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7583-4665","authenticated-orcid":true,"given":"Yuanyuan","family":"Xue","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China."},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3533-3465","authenticated-orcid":true,"given":"Chunlong","family":"Xu","sequence":"additional","affiliation":[{"name":"Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8979-2902","authenticated-orcid":true,"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China."},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China."},{"name":"Department of Otorhinolaryngology, Second Affiliated Hospital, University of South China, Hengyang 421001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China."},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-3094","authenticated-orcid":true,"given":"Runze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China."},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2104-6051","authenticated-orcid":true,"given":"Shuang","family":"Han","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China."},{"name":"Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China."},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China."},{"name":"Department of Otolaryngology Head and Neck Surgery, Second Hospital of Jilin University, Changchun 130000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"Huigene Therapeutics Inc., Shanghai 201315, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng-Lin","family":"Li","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China."},{"name":"NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-6910","authenticated-orcid":true,"given":"Huawei","family":"Li","sequence":"additional","affiliation":[{"name":"ENT Institute and Department of Otorhinolaryngology, Eye &amp; 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