Perfect genomic correction of human iPSCs from Becker Muscular Dystrophy through chromosome transplantation and generation of functional cardiomyocytes

Becker Muscular Dystrophy (BMD) is an X-linked disorder within the dystrophinopathies group, caused by mutations in the DMD gene (chromosome Xp21.2 ) leading to a progressive muscle deterioration. The large size of DMD gene and associated extensive genomic mutations pose challenges for conventional gene therapy. In our laboratory, we developed chromosome tranplantation (CT), a novel genomic tool to fully correct genomic defects such as the DMD gene mutation in induced pluripotent stem cells (iPSCs). CT involves substituting the defective endogenous chromosome with a normal exogenous one, restoring a euploid karyotype in the corrected cells. We applied CT to BMD-iPSCs, and confirmed the functional recovery of dystrophin protein, encoded by the DMD gene, in BMD-affected and corrected cardiomyocytes differentiated from these iPS lines.