Genome Editing To Repair DNA Duplications
Duchenne UK and MDUK are currently co-funding Professor Francesco Muntoni and Dr Francesco Conti of the Institute of Child Health, University College London.
They are aiming to use genome editing to repair mutations in the dystrophin gene caused by the duplication of a sequence of DNA. The type of Duchenne muscular dystrophy that is caused by duplications applies to around 10 to 15 percent of people. This project began in 2015.
What Are Duplications?
Mutations in the dystrophin gene cause DMD, and one of the possible mutations is called a duplication, where part of the gene is repeated, leading to a lack of dystrophin.
In this project Professor Muntoni and Dr Conti will use genome editing to remove the repeated section of the gene. Genome editing uses molecular scissors (enzymes called nucleases), to cut the DNA. Professor Muntoni and Dr Conti have already designed molecular scissors to target the particular dystrophin gene where duplication mutations are most frequently found.
The team will first produce a harmless viruses (lentivirus), to deliver the information for the molecular scissors to the cells, where they will be made. They will then assess how well the mutation is repaired by measuring the amount of full-length dystrophin protein being made by the cells.
The research will be carried out in stored cells from people with Duchenne muscular dystrophy with a duplication.
What Is Happening About Clinical Trials?
This research has not reached the level of a clinical trial yet. However, if successful, the technique could be used to correct the mutation in the dystrophin gene in muscle stem cells taken from people with DMD, which would then be transplanted back into them. This would not create an immune response as it will be using a boy’s own cells. Alternatively, the technique could be used to directly correct the mutation by delivering the molecular scissors into a person’s muscle using a harmless virus such as adeno-associated virus (AAV). In both these treatments the DNA of the person being treated would be permanently corrected - but we are a long way from this currently.
In the future, Professor Muntoni and Dr Conti plan to target other duplications in the dystrophin gene.