Innovative therapeutic strategy for Duchenne Muscular Dystrophy by AAV mediated delivery of artificial transcription factor genes

We designed and engineered an artificial gene named "Jazz" able to up-regulate the expression level of a target gene. The gene that we decided to target and up-regulate is utrophin. Utrophin is very similar to dystrophin and it is able to partially replace the functions of defective dystrophin in Duchenne Muscular Dystrophy (DMD). Over-expression of utrophin gene represents one of the main therapeutic strategies proposed in the last years for the cure of DMD. The artificial gene Jazz is able to up-regulate utrophin in the muscle of a Jazz-transgenic mouse. Moreover, we observed a significant recovery of muscle strength in dystrophic mdx mice crossed with the Jazz-transgenic mice. We are now focusing on three main tasks: 1) to develop small viral vectors, based on "adeno associated virus" that are safe for humans and that can vehicle our Jazz gene in the muscle of dystrophic mdx mice, 2) to develop novel artificial genes with better performances, designed to elude the host immuno-response; 3) to vehicle in the same gene therapy vectors, in addition to Jazz, small molecules named miRs and anti-miRs that could be crucial to achieve utrophin therapeutic levels.