{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:27:53Z","timestamp":1780385273069,"version":"3.54.1"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"794","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,4,16]]},"abstract":"<jats:p>\n            Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by the expansion of a CTG-triplet repeat in the 3\u2032 untranslated region of the\n            <jats:italic>dystrophia myotonica protein kinase<\/jats:italic>\n            (\n            <jats:italic>DMPK<\/jats:italic>\n            ) gene. It results in the transcription of toxic RNAs that contain expanded CUG repeats (CUG\n            <jats:sup>exp<\/jats:sup>\n            ). Splicing factors, such as muscleblind-like 1 (MBNL1), are sequestered by CUG\n            <jats:sup>exp<\/jats:sup>\n            , thereby disrupting the normal splicing program that is essential for various cellular functions. Pentatricopeptide repeat (PPR) proteins, originally found in plants, regulate RNA in organelles by binding in a sequence-specific manner. Here, we designed PPR proteins that specifically bind to the hexamer of CUG repeat RNAs (CUG-PPRs) and showed that CUG-PPR1 could ameliorate RNA toxicity induced by CUG\n            <jats:sup>exp<\/jats:sup>\n            in cell models of DM1. A single systemic recombinant adeno-associated virus (AAV9) vector\u2013mediated gene delivery of CUG-PPR1 demonstrated long-term therapeutic effects on myotonia and restored splicing activity in a mouse model of DM1. These results highlight the potential of PPR molecules to target pathogenic RNA sequences in DM1 and potentially other RNA-mediated disorders.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adq2005","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T18:00:51Z","timestamp":1744826451000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["Pentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse model"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-7544","authenticated-orcid":true,"given":"Takayoshi","family":"Imai","sequence":"first","affiliation":[{"name":"EditForce Inc., Fukuoka 819-0395, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Miyai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Osaka University 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