biostudies-literatureUnknown10(41)Cerro-Herreros EThis study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the <i>DMPK</i> gene, leading to variable clinical manifestations by depleting muscleblind-like splicing regulator protein MBNL1. AntimiRs targeting natural repressors miR-23b and miR-218 boost MBNL1 expression but must be optimized for a better pharmacological profile in humans. In untreated cells, miR-23b and miR-218 were up-regulated, which correlated with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG expansions in <i>DMPK</i>. AntimiR treatment improved RNA toxicity readouts and corrected regulated exon inclusions and myoblast defects such as fusion index and myotScience advanceseadn6525https://www.ebi.ac.uk/biostudies/studies/S-EPMC11463307biostudies-literatureAntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.PMC11463307Suelves MNunez-Manchon JVilchez JJCerro-Herreros EGarcia-Rey ALlamusi BCarrascosa-Saez MPoyatos-Garcia Jde Munain ALMoreno KArtero REspinosa-Espinosa JNaldaiz-Gastesi NNogales-Gadea GLosilla DPGonzalez-Martinez IfalseAntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.This study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the <i>DMPK</i> gene, leading to variable clinical manifestations by depleting muscleblind-like splicing regulator protein MBNL1. AntimiRs targeting natural repressors miR-23b and miR-218 boost MBNL1 expression but must be optimized for a better pharmacological profile in humans. In untreated cells, miR-23b and miR-218 were up-regulated, which correlated with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG expansions in <i>DMPK</i>. AntimiR treatment improved RNA toxicity readouts and corrected regulated exon inclusions and myoblast defects such as fusion index and myot2024-01-01T00:00:00Z2024 Oct2026-07-14T19:43:02.792Z2025-04-04T02:29:38.18ZS-EPMC114633073938322910.1126/sciadv.adn6525