The gene editing technique known as CRISPR is a revolutionary approach to treating inherited diseases. However, the tool has yet to be used to effectively treat long-term, chronic conditions. A research team led by Dongsheng Duan, Ph.D., at the University of Missouri School of Medicine has identified and overcome a barrier in CRISPR gene editing that may lay the foundation for sustained treatments using the technique.
CRISPR gene editing is inspired by the body’s natural defensive ability to fend off viruses. The technology enables researchers to alter DNA sequences by cutting out and replacing a mutation in the genome, which has the potential to treat a variety of genetic diseases and conditions. Duan, along with his collaborators at MU, the National Center for Advancing Translational Sciences at the National Institutes of Health and Duke University, are studying how to harness CRISPR to treat Duchenne muscular dystrophy (DMD).
Children with DMD have a gene mutation that interrupts the production of a protein known as dystrophin. Without dystrophin, muscle cells become weaker and eventually die. Many children lose the ability to walk, and muscles essential for breathing and heart function ultimately stop working.
“CRISPR essentially cuts out the mutation and stitches the gene back together,” said Duan, who serves as the Margaret Proctor Mulligan Professor in medical research in the Department of Molecular Microbiology and Immunology at the MU School of Medicine. “In order to do this, the ‘molecular scissors’ in CRISPR, known as Cas9, must know where to cut. The location to cut is flagged by a molecule called gRNA. We were surprised to find that by increasing the quantity of flags, we could extend the effectiveness of the therapy from three months to 18 months in our mouse model.”