People with Duchenne muscular dystrophy carry a mutation in the DMD gene coding for dystrophin, a protein crucial for proper muscle function. Scientists are working to treat the disease at its genetic root with CRISPR gene editing. Tweaking the ratio of CRISPR gene-editing components can help boost the production of dystrophin, researchers reported March 6 in Science Advances.
CRISPR uses the Cas9 enzyme to snip DNA with instructions on where to cut provided by guide RNA. In this study, the researchers found that equal parts enzyme and guide RNA—targeted at a specific part of the DMD gene—didn’t bump up the production of dystrophin very much. When they used 10 times more guide RNA than Cas9, they found that mice were able to reach roughly 90 percent of the normal dystrophin protein expression in their muscles and hearts four weeks after gene editing. The researchers also used CRISPR gene-editing techniques to restore production of dystrophin in human heart cells affected by Duchenne muscular dystrophy.
Y.-L. Min et al., “CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells,” Science Advances, doi:10.1126/sciadv.aav4324, 2019.