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Researchers have used CRISPR to treat an adult mouse model of Duchenne muscular dystrophy.

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Researchers have used CRISPR to treat an adult mouse model of Duchenne muscular dystrophy. This marks the first time that CRISPR has successfully treated a genetic disease inside a fully developed living mammal with a strategy that has the potential to be translated to human therapy.

Researchers from Duke University had previously used CRISPR to correct genetic mutations in cultured cells from Duchenne patients, and other labs had corrected genes in single-cell embryos in a laboratory environment. But the latter approach is currently unethical to attempt in humans, and the former faces many obstacles in delivering treated cells back to muscle tissues.

Another approach, which involves taking CRISPR directly to the affected tissues through gene therapy techniques, also faces challenges, particularly with delivery. In the new study, Duke University researchers overcame several of these obstacles by using a non-pathogenic carrier called adeno-associated virus, or AAV, to deliver the gene-editing system.

The paper appears on Dec. 31, 2015 in Science.

"Recent discussion about using CRISPR to correct genetic mutations in human embryos has rightfully generated considerable concern regarding the ethical implications of such an approach," said Gersbach, associate professor of biomedical engineering at Duke University. "But using CRISPR to correct genetic mutations in the affected tissues of sick patients is not under debate. These studies show a path where that's possible, but there's still a considerable amount of work to do."

Duchenne muscular dystrophy is caused by problems with the body's ability to produce dystrophin, a long protein chain that binds the interior of a muscle fiber to its surrounding support structure. Dystrophin is coded by a gene containing 79 protein-coding regions, called exons. If any one exon gets a debilitating mutation, the chain does not get built.

Without dystrophin providing support, muscle tends to shred and slowly deteriorate.

Duchenne affects one in 5,000 newborn males. Most patients are wheelchair-bound by age 10 and don't live beyond their 20s or early 30s. The mutation is on the X chromosome so female children with two X chromosomes should have at least one functioning copy of the gene.

Gersbach has been working on potential genetic treatments for Duchenne with various gene-altering systems since starting his lab at Duke in 2009. His lab recently began focusing on CRISPR/Cas9—a modified version of a bacterial defense system that targets and slices apart the DNA of familiar invading viruses.

While Gersbach has had success in cultured patient cells by using a jolt of electricity to punch holes in their membranes to deliver the CRISPR system, this strategy was not practical in a patient's muscle tissues.

"A major hurdle for gene editing is delivery. We know what genes need to be fixed for certain diseases, but getting the gene editing tools where they need to go is a huge challenge," said Chris Nelson, the fellow in Gersbach's laboratory who led the work. "The best way we have to do it right now is to take advantage of viruses, because they have spent billions of years evolving to figure out how to get their own viral genes into cells."

Nelson and Gersbach began working on packaging gene editing tools into AAV—the most popular virus for delivering genes today. They were assisted through collaborations with AAV experts Aravind Asokan, associate professor at the University of North Carolina—Chapel Hill School of Medicine, and Dongsheng Duan at the University of Missouri School of Medicine. Duan also provided significant expertise from a long history of work on gene therapy for neuromuscular disorders.

To use viruses as delivery vehicles for gene therapy, researchers take all the harmful and replicative genes out of the virus and put in the therapeutic genes they want to deliver. While early virus types didn't work well for various reasons, such as integrating into the genome and causing problems or triggering immune responses, AAV thus far has proven special. It's a virus that many people are exposed to anyway and is non-pathogenic, but still exceptionally effective at getting into cells.

AAV is in use in many late-stage clinical trials in the United States, and has already been approved for use in one gene therapy drug in the European Union. There are also different versions of AAV that can preferentially go to different tissues, such as skeletal and cardiac muscle, so researchers can deliver them systemically.

Top Reddit comments:

This has so much potential. Some of it is to save lives, and some to start the eugenics wars. Altogether that's a lot of potential though.


The first human to live for 200 years has probably already been born.

Lenses were to bacteria and astronomy what CRISPR is to genetics. There's no putting this back in the bottle. People are going to live much, much longer. Gene therapy will do to average lifespans in this century what antibiotics food in the last. Advances in anti-ageing have the potential to reverse much of the damage that eventually kills us.

We live in the future.

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