Targeted genome editing in vivo corrects a Dmd duplication restoring wild‐type dystrophin expression

<p class="Paragraph">Tandem duplication mutations are increasingly found to be the direct cause of many rare heritable diseases, accounting for up to 10% of cases. Unfortunately, animal models recapitulating such mutations are scarce, limiting our ability to study them and develop genome editing-based therapies. Here, we describe the generation of the <em>Dup18-30 </em>mouse model, harbouring a multi-exonic tandem duplication in the <i>Dmd</i> gene which recapitulates a human mutation. Duplication correction of this mouse was achieved by implementing a single-guide RNA (sgRNA) CRISPR/Cas9 approach. This strategy precisely removed a duplication mutation <i>in vivo</i>, restored full-length dystrophin expression, and was accompanied by improvements in both histopathological and clinical phenotypes. We conclude that CRISPR/Cas9 represents a powerful tool to accurately model and treat tandem-duplication mutations. </p> <p class="Paragraph">This dataset includes the deep amplicon sequencing analysis performed to detect single-sgRNA/Cas9 off-target and on-target effects in the <em>Dup18-30</em> mice after treatment.</p>