OR09

Myotonic dystrophy type 1 (DM1) is a disease caused by the expansion of CTG repeats in the 3’ untranslated region of the DMPK gene. When transcribed, the expanded mRNA accumulates in the nucleus and forms aggregates that alter the function of RNA-binding proteins, leading to the abnormal splicing of transcripts. To date, there are no curative treatments available for this disease. We have recently developed a CRISPR-Cas9 system to delete the CTG repetitions in the DMPK locus. We are using the DMSXL mouse model, which contains the human DMPK gene carrying up to 1500 CTG repeats, to evaluate the efficacy of this approach in vivo. In this study, DMSXL mice were treated with either a single or dual AAV-CRISPR-Cas9 vectors at birth or at 6 weeks of age, and the effect of the treatment was evaluated at the molecular and histological level. Preliminary results indicate that the two approaches lead to CTG deletion in muscle.