Vaccination breakthroughs in the past few years have shown the potential in messenger ribonucleic acid (mRNA). This tiny molecule naturally resides in every one of our cells and has the important job as the middleman between our DNA and proteins, relaying information from one to the other.
Scientists are now looking into this supermolecule to treat muscular dystrophy, a currently incurable group of diseases that cause progressive weakness and loss of muscle mass. It is only a small mutation in the genome that causes these potentially fatal conditions, with the class of genetic diseases encompassing around 50 disorders.
A team from Max Delbrück Center for Molecular Medicine developed a method to repair this DNA sequence using a CRISPR-Cas9 tool.
Where does mRNA come into this?
Getting the CRISPR-Cas9 machinery into cells is difficult. Normal delivery methods, such as swallowing or injection, aren’t viable. The team instead had the idea of dispatching only the instructions in the form of mRNA molecules. This way, the small piece of genetic information can travel in and use the cell’s own equipment to build itself.
“In the vaccines, the mRNA molecules contain the genetic instructions for building the virus’s spike protein, which the pathogen uses to invade human cells,” explains Christian Stadelmann, a co-lead author of the study “In our work we use mRNA molecules that contain the building instructions for the gene-editing tool.”
How does this treat the disease?
The CRISPR-Cas9 tool works by slightly tweaking the problem spot, not by cutting the DNA. “This allows us to work with even greater precision,” Stadelmann stated. The method worked well in human muscle stem cells, with the results published in Molecular Therapy—Nucleic Acid. This paved the way for clinical trials which will at the end of the year on five to seven patients with a type of muscular dystrophy called muscular atrophy.
“Sufferers who are in wheelchairs won’t just get up and start walking after the therapy. But for many patients, it is already a big step forward when a small muscle that is important for grasping or swallowing functions better again. The idea of repairing larger muscles, such as those needed for standing and walking, is already under consideration,” says Professor Simone Spuler, head of the research lab.
Source study: Molecular Therapy—Nucleic Acid—mRNA-mediated delivery of gene editing tools to human primary muscle stem cells