{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:23:12Z","timestamp":1793726592816,"version":"4.6.1"},"reference-count":28,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,9]]},"abstract":"<jats:p>\n                    Angelman syndrome (AS) is a severe neurodevelopmental disorder for which only symptomatic treatment with limited benefits is available. AS is caused by mutations affecting the maternally inherited ubiquitin protein ligase E3A (\n                    <jats:italic>UBE3A<\/jats:italic>\n                    ) gene. Previous studies showed that the silenced paternal\n                    <jats:italic>Ube3a<\/jats:italic>\n                    gene can be activated by targeting the antisense\n                    <jats:italic>Ube3a-ATS<\/jats:italic>\n                    transcript. We investigated antisense oligonucleotide\u2013induced (ASO-induced)\n                    <jats:italic>Ube3a-ATS<\/jats:italic>\n                    degradation and its ability to induce UBE3A reinstatement and rescue of AS phenotypes in an established\n                    <jats:italic>Ube3a<\/jats:italic>\n                    mouse model. We found that a single intracerebroventricular injection of ASOs at postnatal day 1 (P1) or P21 in AS mice resulted in potent and specific UBE3A reinstatement in the brain, with levels up to 74% of WT levels in the cortex and a full rescue of sensitivity to audiogenic seizures. AS mice treated with ASO at P1 also showed rescue of established AS phenotypes, such as open field and forced swim test behaviors, and significant improvement on the reversed rotarod. Hippocampal plasticity of treated AS mice was comparable to WT but not significantly different from PBS-treated AS mice. No rescue was observed for the marble burying and nest building phenotypes. Our findings highlight the promise of ASO-mediated reactivation of\n                    <jats:italic>UBE3A<\/jats:italic>\n                    as a disease-modifying treatment for AS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.145991","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T16:59:27Z","timestamp":1628614767000},"source":"Crossref","is-referenced-by-count":97,"title":["Antisense oligonucleotide treatment rescues UBE3A expression and multiple phenotypes of an Angelman syndrome mouse model"],"prefix":"10.1172","volume":"6","author":[{"given":"Claudia","family":"Milazzo","sequence":"first","affiliation":[{"name":"Departments of Clinical Genetics and Neuroscience and"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-9259","authenticated-orcid":true,"given":"Edwin J.","family":"Mientjes","sequence":"additional","affiliation":[{"name":"Departments of Clinical Genetics and Neuroscience and"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse","family":"Wallaard","sequence":"additional","affiliation":[{"name":"Departments of Clinical Genetics and Neuroscience and"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5051-2301","authenticated-orcid":true,"given":"S\u00f8ren Vestergaard","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Therapeutic Modalities, Roche Innovation Center Copenhagen, F. Hoffmann-La Roche Ltd., Horsholm, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamille Dumong","family":"Erichsen","sequence":"additional","affiliation":[{"name":"Therapeutic Modalities, Roche Innovation Center Copenhagen, F. Hoffmann-La Roche Ltd., Horsholm, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejaswini","family":"Kakunuri","sequence":"additional","affiliation":[{"name":"Departments of Clinical Genetics and Neuroscience and"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.S. Elise","family":"van der Sman","sequence":"additional","affiliation":[{"name":"Departments of Clinical Genetics and Neuroscience and"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kremer","sequence":"additional","affiliation":[{"name":"Neuroscience and Rare Diseases Discovery & Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan T.","family":"Miller","sequence":"additional","affiliation":[{"name":"Neuroscience and Rare Diseases Discovery & Translational Area, Roche Innovation Center Basel, F. 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