{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:46:35Z","timestamp":1782798395557,"version":"3.54.5"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>\n                    Rett syndrome (RTT) stands at the forefront of the genetic therapy revolution. This severe X-linked neurodevelopmental disorder, primarily caused by mutations in the\n                    <jats:italic>MECP2<\/jats:italic>\n                    gene, was historically considered a static condition but is now recognized as a potentially reversible neurodevelopmental disorder. This review synthesizes recent breakthroughs in our understanding of MeCP2\u2019s role in chromatin architecture, including its involvement in liquid-liquid phase separation (LLPS). We critically examine the transition from conventional symptom management to precision epigenetic therapeutics. Key advances discussed include next-generation gene replacement strategies with autoregulatory control to prevent toxicity, programmable epigenetic editing (e.g., CRISPR-off\/on) to correct\n                    <jats:italic>MECP2<\/jats:italic>\n                    expression endogenously, and novel approaches for X-chromosome reactivation (XCI). Furthermore, we propose a stratified therapeutic framework (genotype-guided therapies) based on specific mutation types. Finally, we analyze data from ongoing clinical trials and highlight the remaining hurdles\u2014such as delivery efficiency, immunogenicity, and the urgent need for objective biomarkers\u2014that must be overcome to translate these epigenetic innovations into a cure.\n                  <\/jats:p>","DOI":"10.3389\/fnbeh.2026.1835425","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:37:38Z","timestamp":1782797858000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials"],"prefix":"10.3389","volume":"20","author":[{"given":"Cuijie","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bocai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]},{"name":"School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou","place":["Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3822","DOI":"10.1016\/j.ymthe.2025.05.011","article-title":"Neuron-targeted gene therapy rescues multiple phenotypes of STXBP1-related disorders in mice and is well tolerated in nonhuman primates.","volume":"33","author":"Aeran","year":"2025","journal-title":"Mol. 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