Abstract Body: Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder that primarily affects skeletal and cardiac muscle. Cardiac conduction defects occur in ~80% of patients, and arrhythmia-associated sudden cardiac death is a major cause of mortality in DM1. DM1 is caused by a CTG repeat expansion in the DMPK gene, generating toxic CUG repeat RNA that forms nuclear foci and sequesters the RNA-binding protein MBNL1, leading to widespread splicing dysregulation. In DM1, aberrant splicing of transcripts encoding ion channels and calcium handling proteins disrupts cardiomyocyte excitability and conduction. Despite advances in understanding disease-associated splicing changes, no approved disease-modifying therapies exist. To address this, we engineered U1 and U7 small nuclear RNAs (snRNAs) to selectively target DMPK CUG repeat RNA in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) harboring ~1,150 CUG repeats. RNA fluorescence in situ hybridization demonstrated that U1 and U7 significantly reduced nuclear foci (p < 0.0001), with orthogonal analysis confirming reduced CUG RNA levels (p < 0.05, U1; p < 0.001, U7) relative to non-targeting controls. RNA sequencing revealed widespread splicing defects in DM1 iPSC-CMs, with >1,750 skipped exon events relative to control iPSC-CMs (FDR < 0.01, ΔPSI > 0.1). Expression of U1 and U7 shifted splicing of key mis-spliced transcripts, including SCN5A, TNNT2, LDB3, INSR, and MBNL1/2, toward control-like splicing patterns. Off-target analysis showed no significant effects on transcripts containing short CUG repeats (BPGM, CTSA, TCF2), indicating specificity for expanded repeat RNA. These findings demonstrate that engineered U1 and U7 snRNAs reduce toxic CUG repeat RNA foci and improve disease-associated splicing in human cardiomyocytes, supporting a programmable RNA-based therapeutic strategy for DM1. This compact, non-immunogenic snRNA-based platform is compatible with adeno-associated viral delivery and is well positioned for therapeutic translation.