{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:42:56Z","timestamp":1792143776788,"version":"4.4.0"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"679","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,1,18]]},"abstract":"<jats:p>\n                    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of methyl CpG-binding protein 2 (\n                    <jats:italic>MECP2<\/jats:italic>\n                    ) on the X chromosome in young females. Reactivation of the silent wild-type\n                    <jats:italic>MECP2<\/jats:italic>\n                    allele from the inactive X chromosome (Xi) represents a promising therapeutic opportunity for female patients with RTT. Here, we applied a multiplex epigenome editing approach to reactivate MECP2 from Xi in RTT human embryonic stem cells (hESCs) and derived neurons. Demethylation of the\n                    <jats:italic>MECP2<\/jats:italic>\n                    promoter by dCas9-Tet1 with target single-guide RNA reactivated MECP2 from Xi in RTT hESCs without detectable off-target effects at the transcriptional level. Neurons derived from methylation-edited RTT hESCs maintained MECP2 reactivation and reversed the smaller soma size and electrophysiological abnormalities, two hallmarks of RTT. In RTT neurons, insulation of the methylation-edited\n                    <jats:italic>MECP2<\/jats:italic>\n                    locus by dCpf1-CTCF (a catalytically dead Cpf1 fused with CCCTC-binding factor) with target CRISPR RNA enhanced MECP2 reactivation and rescued RTT-related neuronal defects, providing a proof-of-concept study for epigenome editing to treat RTT and potentially other dominant X-linked diseases.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.add4666","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T13:58:15Z","timestamp":1674050295000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":99,"title":["Multiplex epigenome editing of\n                    <i>MECP2<\/i>\n                    to rescue Rett syndrome neurons"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0453-489X","authenticated-orcid":true,"given":"Junming","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Physiology and Cellular Biophysics, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1307-7520","authenticated-orcid":true,"given":"Xiaonan","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-6762","authenticated-orcid":true,"given":"Bing","family":"Xie","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-6633","authenticated-orcid":true,"given":"Jacqueline","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-2610","authenticated-orcid":true,"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA."},{"name":"Department of Neurosurgery, Boston Children\u2019s Hospital, Boston, MA 02465, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-6112","authenticated-orcid":true,"given":"Charles H.","family":"Li","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-8899","authenticated-orcid":true,"given":"Henry M.","family":"Colecraft","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-7099","authenticated-orcid":true,"given":"Rudolf","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2799-2519","authenticated-orcid":true,"given":"X. Shawn","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cellular Biophysics, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, USA."},{"name":"Columbia Stem Cell Initiative, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, USA."},{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, Columbia University, New\u00a0York, NY 10032, 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