In partnership, the Myotonic Dystrophy Foundation US and the Myotonic Dystrophy Foundation UK made the following grants in 2019:

“Developing novel CRISPR-Cas9 variants for efficient in vivo contraction of CTG/CAG repeats”

PI: Vincent Dion, PhD
Cardiff University, Wales, UK

Gene editing, a way to correct the mutation that causes DM1, provides novel research avenues. Recently, Dr. Dion’s team showed that CRISPR-Cas9, an unparalleled gene editing technology, can contract precisely the expanded CTG/CAG repeat tract, thereby removing the cause of DM1. They found that gently nicking the repeat tract leads to contractions. Administration of the enzyme is difficult and inefficient because it is too large to be packaged into adenoassociated viruses, the delivery method of choice for gene therapies. In this project, they aim to improve the efficiency of Cas9 delivery by reducing the size of the enzyme and to determine its safety by measuring the frequency of unwanted mutations it might cause. Dion will test new Cas9 variants both in human cells and in pre-clinical mouse models. They aim to develop a safe and efficient tool for an eventual therapy based on gene editing.