Highly Specific DMPK-promoter targeted by CRISPRi reverses DM1-associated defects in patient muscle cells

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that originates from an expansion of CTG microsatellites in the 3' untranslated region of the DMPK gene,thus leading to the expression of transcripts containing expanded CUG repeats (CUGexp).In this study, we investigated a DMPK-promoter silencing strategy using CRISPR interference as a new alternative approach. The most effective guides allowed to reduce the level of DMPK transcripts and CUGexp-RNA aggregates up to 80%. CRISPRi-mediating transcriptional CUGexp-DMPK repression corrects the overall transcriptome of DM1 muscle cells including spliceopathy and reverses physiological parameters in disease cells.