A new study published in Circulation Research found that clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing reduced heart abnormalities in mouse and human models of Duchenne muscular dystrophy (DMD). This was the case regardless of how the reading frame of the mutated DMD gene was restored.

“These findings provide key insights into the utility of genome editing as a novel therapeutic for DMD-associated cardiomyopathy,” Ayhan Atmanli, MD, PhD, and the coauthors of the study stated.

With advances in the respiratory management of patients with DMD, cardiomyopathy has increasingly become an important aspect of the disease that needs to be tackled.

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To define the effects of CRISPR/Cas9 genome editing on heart abnormalities in DMD, a team of researchers from the University of Texas Southwestern Medical Center, Dallas, used pluripotent stem cells (iPSCs) from a patient with DMD and his healthy brother, as well as from a mouse model of DMD. The patient had a deletion in exon 44 of the DMD gene. Using CRISPR/Cas9 genome editing, the researchers corrected the reading frame of the gene by either reframing or exon skipping. 

They found that cardiomyocytes derived from iPSCs in which the reading frame was not restored had morphologic, structural, and functional deficits compared to the control cardiomyocytes. However, cardiomyocytes obtained from DMD iPSCs in which the reading frame was restored using either method (reframing or exon skipping) were similar to the control cardiomyocytes, with no abnormalities. 

When they conducted bulk-RNA sequencing, the researchers found that cardiomyocytes derived from DMD iPSCs showed transcriptional dysregulation that is consistent with dilated cardiomyopathy. This was reduced in cardiomyocytes obtained from DMD iPSCs in which the reading frame of the gene was restored.

The researchers also showed that if they used CRISPR/Cas9 genome editing in already differentiated cardiomyocytes, the arrhythmogenic potential of the treatment was reduced. 

Finally, they showed that the transcriptional dysregulation present in the cardiomyocytes and fibroblasts of DMD mice was reduced when the reading frame of the gene was corrected in the animals using the CRISPR/Cas9 approach.

The researchers concluded that genome editing could be a novel therapeutic approach for DMD-associated cardiomyopathy.


Atmanli A, Chai AC, Cui M, et al. Cardiac myoediting attenuates cardiac abnormalities in human and mouse models of Duchenne muscular dystrophy. Circ Res. Published online August 10, 2021. doi:10.1161/CIRCRESAHA.121.319579