Researchers from Duke University used CRISPR gene editing to correct the genetic disease called Duchenne Muscular Dystrophy, or DMD, in mice.
The team observed that the technology can safely correct DMD and remain stable for more than a year. They hope that the study will lead to the use of gene editing for human therapy in the future.
The researchers published a paper titled "Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy" in the journal Nature Medicine on Monday, Feb. 18.
Gene Editing As Treatment For Muscular Dystrophy In Mice
DMD is a rare genetic disease that occurs when cells within the body cannot make dystrophin, leading to muscle weakness that gets worse over time. Many patients who are diagnosed with the disease are wheelchair-bound by the age of 10 and do not live beyond their early 30s.
There currently is no cure for DMD, but several researchers, including Charles Gersbach, a professor at Duke University, have been exploring the possibility of using gene editing for treatment of genetic diseases.
In their new research, the team led by Gersbach used the CRISPR/Cas9 tool to snip the dystrophin exon from the mutation to allow the DNA's natural system to stitch the remaining gene back together. The result is a shortened but functional dystrophin gene.
During the experiment, the researchers administered CRISPR therapy to adult and newborn mice. For a year, they measured how many muscle cells were successfully edited and monitored the genetic alterations that occurred. They also took note of the immune system's response to the CRISPR protein Cas9, which acts as the scissors that make "cuts" to the genome.
For the first eight weeks, the researchers found that functional dystrophin was restored in mice, resulting to an increase of muscle strength.
The team did observe a response from the Cas9, but they said it did not result to death of mice. It also did not interfere with the therapy's ability to edit the dystrophin gene.
The researchers also observed that two-day-old mice that received the therapy showed no immune response. In some cases, they found that the CRISPR gene editing strengthened over the course of the year.
Toward The Treatment Of DMD
Gersbach and his team stated that the goal of the study was to explore potential long-term consequences of gene editing as treatment of genetic diseases, particularly DMD.
"It is widely believed that gene editing leads to permanent gene correction," he stated. "However, it's important to explore theoretical possibilities that could undermine the effects of gene editing, such as losing treated cells or an immune response."
Christopher Nelson, a postdoctoral fellow at the university, added that their findings suggest that the immune system's response to the Cas9 should further be explored as researchers move to testing CRISPR among other animal models and, eventually, humans.
Gersbach has been working on a potential treatment for DMD using CRISPR since 2009. In 2016, he and his team published one of the first "successful uses of CRISPR to treat an animal model of [a] genetic disease."