Duchenne muscular dystrophy is one of the most common fatal genetic diseases. It causes muscle degeneration and eventually death due to weakened heart and lung muscles.

Several new experiments published in Science demonstrate that we can now edit the genomes of mice with muscular dystrophy, effectively restoring a large portion of function in the heart and other muscles. These experiments show exciting promise for the use of CRISPR in mammalian gene editing, which could eventually lead to cures for this and other genetic diseases in humans.

Muscular dystrophy is a group of diseases that result in muscle weakness in involuntary and voluntary muscles. Often, this weakness is accompanied by muscle cell death. The specific disorder examined in this study is Duchenne muscular dystrophy, named after the French neurologist who first identified it. It’s a recessive form of dystrophy caused by mutations in the gene dystrophin, which is located on the X-chromosome. Because this is an X-linked recessive disease, it is more common in boys than girls—boys only have one copy of the X chromosome, so if their one copy carries the mutation, they will have the disease.

The gene dystrophin encodes the dystrophin protein, which plays an important role in muscle tissues. The most common mutations in this gene are deletions that shift the DNA code, so that cells can no longer manufacture the protein correctly. Since Duchenne muscular dystrophy is caused by a very specific type of mutation on a single gene, it is a strong candidate for correction via gene editing.

The CRISPR system allows for live gene editing using a virus to insert DNA into a cell. The DNA needs to encode three things: the gene for Cas9, which cuts DNA; RNA that guides Cas9 to the right place to cut; and a DNA template to repair this cut. For this study, to treat Duchenne muscular dystrophy in mice, CRISPR was used to cut and repair the mutated dystrophin gene (specifically, the researchers deleted the exon that carries the mutation). The editing was done in mouse muscle cells, in two-day-old mice, and in adult mice.

After treatment with CRISPR, more than half of mouse samples showed that the appropriate gene had been edited. Additionally, more than half of the sampled muscle cells were expressing the dystrophin protein. The muscle that received the CRISPR treatment also showed significant improvements in function.

The use of CRISPR on mouse pups restored dystrophin protein expression in the heart and lung muscles. This is particularly important because the degradation of heart and lung muscles is typically the final cause of death in human patients with Duchenne muscular dystrophy. CRISPR treatment of adult mice with this disorder also induced expression of the dystrophin protein in heart tissue. This means that, after CRISPR treatment, adult mice that had lived their whole lives without a functioning dystrophin protein suddenly began to express it in their cardiac muscle.

Other papers in this issue of Science supported these findings and presented details on increased muscle strength in adolescent mice treated with CRISPR, in addition to demonstrating that the CRISPR complex can be delivered locally to specific muscles.

Combined, these studies show a promising new application for CRISPR gene editing in treating Duchenne muscular dystrophy and may give hope to the thousands of humans currently living with this fatal disease. If doctors are eventually able to use this system to induce dystrophin expression in afflicted humans, their life spans and quality of life many be considerably improved. And there are a number of additional diseases with the same sort of simple genetics that would make them amenable to similar treatments.

However, CRISPR is still a very new genetic therapy, and its use in humans is not currently approved. Therefore, many more studies will need to be conducted before we try this on people.

Science, 2015. DOI: 10.1126/science.aad5143 (About DOIs).