{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:39:13Z","timestamp":1782877153473,"version":"3.54.5"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,11]]},"abstract":"<jats:p>\n            Pathogenic RNA splicing variants have emerged as promising therapeutic targets due to their role in disease while preserving coding sequences. In this study, we developed RECTAS-2.0, a small molecule designed to correct RNA mis-splicing caused by the\n            <jats:italic>GLA<\/jats:italic>\n            c.639+919G&gt;A mutation, which leads to the inclusion of a 57-nucleotide poison exon, resulting in later-onset Fabry disease, particularly prevalent in East Asia. RECTAS-2.0 restored normal\n            <jats:italic>GLA<\/jats:italic>\n            mRNA splicing and \u03b1-galactosidase activity in patient-derived B-lymphoblastoid cell lines and induced pluripotent stem cell\u2013derived cardiomyocytes. Furthermore, oral administration of RECTAS-2.0 effectively corrected splicing in a transgenic mouse model, demonstrating its substantial splice-switching activity and safety for clinical application. RECTAS-2.0 demonstrated potential applicability to other genetic disorders that involve similar exon competition. These findings underscore the therapeutic potential of RECTAS-2.0 for Fabry disease and highlight its broader implications for RNA splicing\u2013targeted therapies in genetic disorders.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt9695","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T17:58:41Z","timestamp":1744221521000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-3172","authenticated-orcid":true,"given":"Tomonari","family":"Awaya","sequence":"first","affiliation":[{"name":"Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7079-4788","authenticated-orcid":true,"given":"Masahiko","family":"Ajiro","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."},{"name":"Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."},{"name":"Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruo","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."},{"name":"Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentoku","family":"Gotanda","sequence":"additional","affiliation":[{"name":"Modality Research Laboratories III, Shinagawa R&amp;D Center, Daiichi Sankyo Co. Ltd., Tokyo 140-8710, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Noji","sequence":"additional","affiliation":[{"name":"Modality Research Laboratories I, Shinagawa R&amp;D Center, Daiichi Sankyo Co. Ltd., Tokyo 140-8710, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Modality Research Laboratories I, Shinagawa R&amp;D Center, Daiichi Sankyo Co. 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