Cardiomyocytes from patients with Duchenne muscular dystrophy (DMD) corrected by CRISPR-Cpf1 reframing during stemness (right) show restored dystrophin expression (red), compared to uncorrected cells (left). SCIENCE ADVANCES, Y. ZHANG ET AL. Researchers have been studying the CRISPR-Cas9 gene-editing system as a potential therapeutic tool to modify or delete pathogenic sequences within the human genome. Now, using a more recently discovered system, CRISPR-Cpf1, researchers have demonstrated its utility in correcting disease-causing mutations within the human and mouse genomes. In a paper published today (April 12) in Science Advances, a team led by researchers at the University of Texas (UT) Southwestern Medical Center described how it corrected Duchenne muscular dystrophy (DMD)–causing mutations in patient-derived stem cells and in a mouse model of the disease. Cpf1-based gene editing was able to at least partially restore function in cultures heart muscle cells derived from a DMD patient. The work is a proof of the concept that CRISPR-Cpf1 gene editing could be further developed to correct other disease-causing mutations.
“The authors use CRISPR-Cfp1 to correct the Dmd mutation in vitro and ex vivo,” Harvard Stem Cell Institute’s Amy Wagers, who was not involved in the work, wrote in an email to The Scientist. “This study nicely adds to the repertoire of tools available for Dmd editing, showing that Cpf1—like Cas9 nucleases evaluated in prior studies—is also effective for targeting frame-disrupting mutations in Dmd.”
“This exciting work offers another gene-editing reagent that could potentially be used in clinical settings in the future,” said Renzhi Han, who studies the molecular mechanisms of muscular dystrophies at the Ohio State University Medical Center and also was not involved in the study.
DMD, a fatal X-linked disease that results in progressively weakened skeletal and heart muscles, is caused by ...
