{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:24:54Z","timestamp":1791984294644,"version":"4.4.0"},"reference-count":44,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"846","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35NS097974"],"award-info":[{"award-number":["R35NS097974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic toggle=\"yes\">HNRNPH2<\/jats:italic>\n                    cause an X-linked disorder characterized by developmental delay, intellectual disability, motor and gait disturbances, and seizures. Murine models that reproduce key clinical features of\n                    <jats:italic toggle=\"yes\">HNRNPH2<\/jats:italic>\n                    -related neurodevelopmental disorder suggest that it may result from a toxic gain of function of the mutant protein or a complex loss of normal HNRNPH2 function with impaired compensation by its paralog, HNRNPH1. In this study, we tested gapmer antisense oligonucleotides (ASOs) that target murine\n                    <jats:italic toggle=\"yes\">Hnrnph2<\/jats:italic>\n                    in a non\u2013allele-specific manner. The lead ASO reduced\n                    <jats:italic toggle=\"yes\">Hnrnph2<\/jats:italic>\n                    messenger RNA (mRNA) and protein expression while inducing compensatory up-regulation of\n                    <jats:italic toggle=\"yes\">Hnrnph1<\/jats:italic>\n                    expression in both wild-type and\n                    <jats:italic toggle=\"yes\">Hnrnph2<\/jats:italic>\n                    mutant mouse brains. A single intracerebroventricular injection of the\n                    <jats:italic toggle=\"yes\">Hnrnph2<\/jats:italic>\n                    ASO into neonatal mutant\n                    <jats:italic toggle=\"yes\">Hnrnph2<\/jats:italic>\n                    mice rescued molecular and audiogenic seizure phenotypes and improved certain motor and cognitive phenotypes. ASO treatment at the juvenile stage also rescued audiogenic seizures. In contrast,\n                    <jats:italic toggle=\"yes\">Hnrnph2<\/jats:italic>\n                    ASO administration did not alter survival, body weight, or the incidence of hydrocephalus. In human induced pluripotent stem cell\u2013derived neurons, a human-specific\n                    <jats:italic toggle=\"yes\">HNRNPH2<\/jats:italic>\n                    research ASO reduced\n                    <jats:italic toggle=\"yes\">HNRNPH2<\/jats:italic>\n                    mRNA and up-regulated\n                    <jats:italic toggle=\"yes\">HNRNPH1<\/jats:italic>\n                    mRNA. Mechanistically, we found that\n                    <jats:italic toggle=\"yes\">HNRNPH1<\/jats:italic>\n                    expression is regulated by alternative splicing and that HNRNPH2 modulates this process. These findings provide a preclinical proof of concept for\n                    <jats:italic toggle=\"yes\">HNRNPH2<\/jats:italic>\n                    ASO therapy and offer insights into its underlying molecular mechanism.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adx3491","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:58:42Z","timestamp":1776880722000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Preclinical evaluation of antisense oligonucleotide therapy in a mouse model of\n                    <i>HNRNPH2<\/i>\n                    -related neurodevelopmental disorder"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7189-254X","authenticated-orcid":true,"given":"Ane","family":"Korff","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4229-6161","authenticated-orcid":true,"given":"Xiaojing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9615-606X","authenticated-orcid":true,"given":"Ananya","family":"Samanta","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8751-9216","authenticated-orcid":true,"given":"Yong-Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Patni","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso J.","family":"Lavado","sequence":"additional","affiliation":[{"name":"Center for Pediatric Neurological Disease Research, Pediatric Translational Neuroscience Initiative, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-3101","authenticated-orcid":true,"given":"Anoop Murthy","family":"Kavirayani","sequence":"additional","affiliation":[{"name":"Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ochaba","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA 92010, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2001-3752","authenticated-orcid":true,"given":"Berit","family":"Powers","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA 92010, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-6251","authenticated-orcid":true,"given":"C. Frank","family":"Bennett","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA 92010, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-1612","authenticated-orcid":true,"given":"Hong Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Paul","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.028"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1788"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00230-09"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000551"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62549"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-021-02412-x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61388"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13580"},{"key":"e_1_3_2_10_2","unstructured":"S. Madhok J. 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