utrophin up-regulation by an artificial transcription factor in transgenic mice拉到老年病的人工转录因子转基因小鼠.pdfVIP

Utrophin Up-Regulation by an Artificial Transcription Factor in Transgenic Mice 1,2 3 1,4 1 1 3 3,4 Elisabetta Mattei , Nicoletta Corbi , Maria Grazia Di Certo , Georgios Strimpakos , Cinzia Severini , Annalisa Onori , Agata Desantis , 3 3 4,5 2,5 6 6 2,3 Valentina Libri , Serena Buontempo , Aristide Floridi , Maurizio Fanciulli , Dilair Baban , Kay E. Davies , Claudio Passananti * 1 Istituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche, European Brain Research Institute, Rome, Italy, 2 Italian Association for Cancer Research, Roman Oncogenomic Center, Rome, Italy, 3 Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Regina Elena Cancer Institute, Rome, Italy, 4 Department of Experimental Medicine, University of L’Aquila, L’Aquila, Italy, 5 Laboratory B, Regina Elena Cancer Institute, Rome, Italy, 6 Department of Physiology, Anatomy and Genetics, Medical Research Council Functional Genetics Unit, University of Oxford, Oxford, United Kingdom Duchenne Muscular Dystrophy (DMD) is a severe muscle degenerative disease, due to absence of dystrophin. There is currently no effective treatment for DMD. Our aim is to up-regulate the expression level of the dystrophin related gene utrophin in DMD, complementing in this way the lack of dystrophin functions. To this end we designed and engineered several synthetic zinc finger based transcription factors. In particular, we have previously shown that the artificial three zinc finger protein named Jazz, fused with the appropriate effector domain, is able to drive the transcription of a test gene from the utrophin promoter