{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:26:09Z","timestamp":1791293169462,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DA36895"],"award-info":[{"award-number":["R01-DA36895"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rett Syndrome Research Trust","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Simon Research Foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"FWO - Belgium","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100001491","name":"BAEF","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001491","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,1,23]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The X-chromosome harbors hundreds of disease genes, a subset of which gives rise to neurodevelopmental disorders such as Rett syndrome (RTT), fragile X syndrome, and CDKL5 syndrome. There is presently no disease-specific treatment. Here, we work toward a therapeutic program based on reactivation of the silent X chromosome to restore expression of the missing protein. We develop a mixed modality approach that combines a small-molecule inhibitor of DNA methylation and an antisense oligonucleotide against Xist RNA. This combination achieves up to 30,000-fold methyl-CpG binding protein 2 upregulation in cultured cells. In vivo modeling using a conditional\n                    <jats:italic>Xist<\/jats:italic>\n                    knockout and 5-aza-2\u2032-deoxycytidine recapitulates inactive X reactivation. These findings provide proof of concept for the mixed modality approach to treat X-linked disorders, including RTT.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1715124115","type":"journal-article","created":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T14:37:03Z","timestamp":1514385423000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders"],"prefix":"10.1073","volume":"115","author":[{"given":"Lieselot L. G.","family":"Carrette","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115;"},{"name":"Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyao","family":"Wei","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Press","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Raymond J.","family":"Kelleher","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannie T.","family":"Lee","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,12,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev-genet-110711-155454","article-title":"Dosage compensation of the sex chromosomes","volume":"46","author":"Disteche CM","year":"2012","unstructured":"CM Disteche, Dosage compensation of the sex chromosomes. 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