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. (Representational Image)
Scientists, including one of Indian-origin, have successfully used a gene editing tool to treat a genetic disease in a fully developed living mammal for the first time, an advance that may be translated in humans.
Researchers from Duke University in US used CRISPR to treat an adult mouse model of Duchenne muscular dystrophy.
They 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.
Researchers including Aravind Asokan, associate professor at the University of North Carolina, overcame several of these obstacles by using a non-pathogenic carrier called adeno-associated virus, or AAV, to deliver the gene-editing system.
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 fibre 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 do not live beyond their 20s or early 30s, the researchers said.
The mutation is on the X chromosome so female children with two X chromosomes should have at least one functioning copy of the gene.
"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 from Duke University 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 said.
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.
AAV is in use in many late-stage clinical trials in the US, 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. The study was published in the journal Science.