{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:05:57Z","timestamp":1791947157100,"version":"4.3.4"},"reference-count":35,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). After gene transfer in mice, exogenous MeCP2 expression must be regulated to avoid dose-dependent toxicity. &lt;b&gt;&lt;i&gt;Summary:&lt;\/i&gt;&lt;\/b&gt; The preclinical gene therapy literature for treating RTT illustrates a duly diligent progression that begins with proof-of-concept studies and advances toward the development of safer, regulated &lt;i&gt;MECP2&lt;\/i&gt; viral genome designs. This design progression was partly achieved through international collaborative studies. In 2023, clinicians administered investigational gene therapies for RTT to patients a decade after the first preclinical gene therapy publications for RTT (clinical trial numbers NCT05606614 and NCT05898620). As clinicians take on a more prominent role in &lt;i&gt;MECP2&lt;\/i&gt; gene therapy research, preclinical researchers may continue to test more nuanced hypotheses regarding the safety, efficacy, and mechanism of &lt;i&gt;MECP2&lt;\/i&gt; gene transfer. &lt;b&gt;&lt;i&gt;Key Message:&lt;\/i&gt;&lt;\/b&gt; This review summarizes the history of preclinical &lt;i&gt;MECP2&lt;\/i&gt; gene transfer for treating RTT and acknowledges major contributions among colleagues in the field. The first clinical injections are a shared milestone. <\/jats:p>","DOI":"10.1159\/000539267","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T21:00:38Z","timestamp":1715288438000},"page":"1-10","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome"],"prefix":"10.1159","author":[{"given":"Indumathy","family":"Jagadeeswaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyoung","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Sinnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S371483"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab182"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.10.004"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4406"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179610"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2021.05.013"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1917"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1854-13.2013"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.200"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.04.006"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.04.007"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.12.009"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52629"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3390\/genes15010031"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.22"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(02)00878-8"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.07.013"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.171"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105235"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225206"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.02.016"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.001"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2015.02.007"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nature24058"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1038\/85899"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.011007"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138389"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy159"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090645"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/nn2010"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0600-12.2013"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088685"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.109"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1080\/17482960701856300"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.93"}],"container-title":["Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/dne\/article-pdf\/doi\/10.1159\/000539267\/4245201\/000539267.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/dne\/article-pdf\/doi\/10.1159\/000539267\/4245201\/000539267.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:20:12Z","timestamp":1745421612000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000539267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":35,"URL":"https:\/\/doi.org\/10.1159\/000539267","archive":["Portico"],"relation":{},"ISSN":["0378-5866","1421-9859"],"issn-type":[{"value":"0378-5866","type":"print"},{"value":"1421-9859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,9]]}}}