Scientists corrected the defective genes of Duchenne muscular dystrophy disease by genome editing
Duchenne muscular dystrophy (DMD) is a devastating progressive disease that usually starts in early childhood. DMD occurs because of a mutated gene which fails to produce dystrophin, a protein which is important for the normal structure and function of muscle. Currently, no definitive treatments are available except for palliative therapy, which can only delay the symptoms of the disease. Moreover, available treatments are not completely effective, as they treat just one aspect of the disease, and they may have side effects in the long run.
These days, there has been great interest in developing stem cell and genetic approaches to treat DMD. In one of our previous blogs we have mentioned that injection of cardiac stem cells may have therapeutic potential to heal the heart damage caused by Duchenne muscular dystrophy. Recently, scientists at the University of Kyoto demonstrated that induced pluripotent stem (iPS) cells may be used to correct genetic mutations that cause Duchenne muscular dystrophy .
Another study provides a proof-of-concept of gene therapy using iPS cell technology along with genome editing technique to treat DMD. In this study, Dr Akitsu Hotta and his team demonstrated that it is feasible to correct the mutation in the dystrophin gene using techniques such as TALEN and CRISPR. During the past few years, genome editing by TALEN and CRISPR has emerged as a powerful tool that enables investigators to manipulate virtually any gene in a diverse range of cell types and organisms. The technology is based on the use of engineered nucleases that allow the editing of the genome by cutting genomic sequences at specific locations. However, the safety of such nuclease treatment must be determined before it can be used as a therapeutic in clinics.
The scientists used patient-specific induced pluripotent stem cells (iPS cells) to test three different genome-editing procedures in order to correct the dystrophin gene mutation. Their results demonstrated that genetic correction by these approaches considerably lowers the risk of off-target mutagenesis and thus holds promise for DMD gene therapy. They further showed that genetically corrected iPSCs cells were able to differentiate into skeletal muscle cells and successfully express full-length dystrophin protein. This encouraging data provide an important lead for developing iPSC-based gene therapy for genetic disorders using engineered nucleases, and this approach could be applied to correct mutations for other genetic-based diseases.
 Precise correction of the dystrophin gene in Duchenne Muscular Dystrophy patient-derived iPS cells by TALEN and CRISPR-Cas9, Stem Cell Reports, 2014