Grant: Project Grant

Duchenne muscular dystrophy (DMD) is a most common and devastating genetic disease. People with DMD usually die at 25 to 30 years of age from effects of muscle deterioration. A most promising strategy to treat DMD is a molecular therapy called exon skipping. Exon skipping uses a short DNA-like molecule that acts like a stitch in RNA, an important biological molecule that functions to convert the genetic information of DNA into proteins, to bypass the mutations that cause DMD. With this DNA stitch in place, people with DMD may be able to produce short working versions of their mutated protein in DMD. The first drug in this class of DNA-stitch molecules was approved in 2016. However, two problems have not been solved. First, people with DMD who were given this drug did not have their DMD symptoms improve. Second, this drug can only help around 13% of people with DMD-people with only some types of DNA mutations. Our research will first work to improve the effectiveness of exon skipping for DMD. We are creating the next generation of these DNA-like molecules to be more effective in humans. We will also work to expand number of people with DMD who can be helped by exon skipping therapy. We will experiment with a cocktail of DNA-like molecules that could help 63% people with DMD. Lastly, we will work to understand the mechanisms of how our DNA-like molecules affect the DMD gene. This will help us design a better cocktail of DNA-like molecules. Our DNA-stitching technology could create new therapies for DMD and improved quality of life for people with DMD.