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To date, there are no specific treatment options for DCM patients but heart transplantation. Here, we show the beneficial potential of reframing titin transcripts by antisense oligonucleotide (AON)\u2010mediated exon skipping in human and murine models of DCM carrying a previously identified autosomal\u2010dominant frameshift mutation in\n                    <jats:italic>titin<\/jats:italic>\n                    exon 326. Correction of\n                    <jats:italic>TTN<\/jats:italic>\n                    reading frame in patient\u2010specific cardiomyocytes derived from induced pluripotent stem cells rescued defective myofibril assembly and stability and normalized the sarcomeric protein expression. AON treatment in\n                    <jats:italic>Ttn<\/jats:italic>\n                    knock\u2010in mice improved sarcomere formation and contractile performance in homozygous embryos and prevented the development of the DCM phenotype in heterozygous animals. These results demonstrate that disruption of the\n                    <jats:italic>titin<\/jats:italic>\n                    reading frame due to a truncating DCM mutation can\u00a0be restored by exon skipping in both patient cardiomyocytes\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and mouse heart\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    , indicating RNA\u2010based strategies as a potential treatment option for DCM.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201505047","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T20:52:11Z","timestamp":1426020731000},"page":"562-576","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Antisense\u2010mediated exon skipping: a therapeutic strategy for titin\u2010based dilated cardiomyopathy"],"prefix":"10.1038","volume":"7","author":[{"given":"Michael","family":"Gramlich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna Simona","family":"Pane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Murgia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Sch\u00f6tterl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Goedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Metzger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Brade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Parrotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Gerull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Thierfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Aartsma\u2010Rus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Labeit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Atherton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"McGaughran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sinnecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Ludwig","family":"Laugwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinrad Paul","family":"Gawaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"BFEMMM201505047_CR1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4161\/rna.7.4.12264","volume":"7","author":"A Aartsma\u2010Rus","year":"2010","unstructured":"Aartsma\u2010Rus A (2010) Antisense\u2010mediated modulation of splicing: therapeutic implications for Duchenne muscular dystrophy. 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