Grant: Operating Grant

Duchenne Muscular Dystrophy is due to mutations in a gene coding for a protein called dystrophin, a protein normally located under the plasma membrane of the muscle fibers. In 70% of the patients, the mutation is a deletion of one or several exons. These deletions are such that the total number of nucleotides, which are deleted is not a multiple of 3 nucleotides. To translate the genetic code into proteins, a group of 3 nucleotides called a codon permits to identify the right amino acid to include in the protein. When there is a deletion, which is not a multiple of 3 nucleotides, the codons are changed and thus the amino acids that are included in the protein are changed. Moreover, a stop codon is eventually met and the synthesis of the protein is terminated prematurely. This incomplete dystrophin protein cannot attach to a group of proteins that are in the membrane. The present application aims to modify the dystrophin gene using Zinc Finger Nucleases and Tal effector nucleases to restore the expression of a dystrophin protein, which will be missing some parts but which will be nevertheless functional.