Gene therapy for Duchenne Muscular DystrophyThe idea of gene therapy is to genetically alter humans in order to treat a disease. This involves the delivery of functional genes that could ‘correct’ the mutant or disease genes of the patient.

Royal Holloway is part of a worldwide collaboration to develop a treatment for this devastating condition. Research there has led to the development of a gene therapy solution which is now at the clinical trial stage.

Duchenne Muscular Dystrophy is a neuromuscular disease caused by a defect in the gene coding for the protein dystrophin. This leads to a progressive loss of muscle fibres.

Progressive loss of muscle fibres

The method uses safe Adeno-associated viruses (AAV) which carry the human gene, in place of one of their own genes, into a cell. In some cells, the gene becomes inserted into a chromosome in the nucleus.

However, the dystrophin gene is too large to be packaged inside AAVso dystrophin microgenes, excluding domains dispensable for the functionality of the protein, were designed.

Full length dystrophin gene Microgene for dystrophin

Micro-dystrophin genes are small enough to be carried inside the virus.

Micro-dystrophins are functional, re-activate the dystrophin complex at the muscle fibre membrane and yield sustained improvements.

Cross section of muscular dystrophy muscle �bres 8 weeks after after the muscle was injected with AAV containing the dystrophin microgene.

The microdystrophin protein, stained red, is expressed from the microgene in �bres that were “transformed” by the AAV and these �bres show healthy development. Untransformed �bres, stained green, show damage due to dystrophin de�ciency.

royalholloway.ac.uk/breakthrough