Experimental gene therapy of Duchenne Muscular Dystrophy by artificial transcription factors upregulating the dystrophin-related gene Utrophin

Our project is based on the construction of synthetic genes designed to upregulate the expression level of utrophin, a protein very similar to dystrophin and able to replace the functions of defective dystrophin in Duchenne Muscular Dystrophy (DMD). Overexpression of utrophin gene represents one of the main therapeutic strategies proposed in the last years for the cure of DMD. We designed and engineered a new transcription factor gene, named "Jazz" that has demonstrated able to successfully upregulate utrophin in the muscles of a transgenic mouse model. Moreover we observed a significant recovery of muscle strength in dystrophic mdx mice crossed with the Jazz transgenic mice. Starting from these positive results, we plan to developed even more suitable Jazz-based zinc finger transcription factors to test, directly on mdx dystrophic mice, the feasibility and efficacy of a gene therapy of DMD with these molecules.