New journal publication details in vivo activity of Cellectis’ Meganucleases in muscle fibers
Paris, April 15, 2010 – Cellectis (Alternext: ALCLS), the French Genome engineering specialist, announces today that new data has been published in the scientific journal gene Therapy[1]. Scientists of CellGene inc. and of the Centre Hospitalier Universitaire de Quebec used Meganucleases designed by Cellectis to restore expression of micro-dystrophin in human myoblasts in vitro and in muscle fibers in vivo, providing proof of principle that Meganucleases could be used to efficiently treat Duchenne muscular dystrophy (DMD).
DMD is a hereditary disease caused by mutations of the dystrophin gene, which leads to the production of truncated dystrophin proteins that cannot play their functional role. DMD is a severe recessive X-linked form of muscular dystrophy characterized by rapid progression of muscle degeneration, eventually leading to loss of mobility and death. This affliction affects one in 3,500 males, making it the most prevalent of muscular dystrophies.
In the article published today, Jacques Tremblay and his team used a specific vector (plasmid) coding for dog micro-dystrophin, in which they have inserted gene sequences containing a meganuclease target and modifying the reading frame of the dystrophin gene. A successful genetic event would thus be required to restore expression of an active protein. The data showed that expressed Meganucleases efficiently restored expression of the micro-dystrophin protein, both in vitro (293FT cells and human myoblasts) as well as in vivo (Tibialis anterior muscles of Rag/mdx mice, a model of DMD). Subsequent analysis of the human myoblasts using PCR amplification showed that Meganucleases were able to modify a sufficient number of micro-dystrophin genes to make this approach feasible for application in patients.
“Though clinical applications of Meganucleases to treat Duchenne muscular dystrophy will take many years of additional research, we think that these data provide proof of principle for a potential therapeutic approach to treat not only this debilitating disease but eventually many other hereditary diseases”, declared Jacques Tremblay, of the Human Genetic Unit at the CHUQ.
“Meganucleases, these new tools for DNA surgery, open a new era of gene therapy. The new genetic target proposed by Pr Tremblay and his team fits in one of the therapeutic objectives set by AFM (the French Muscular Dystrophy Association) and Cellectis. We’re still a long way from the clinical evaluation of such a strategy but we’ve put all our common efforts to reach it”, declared Serge Braun, AFM Chief Scientific Officer. AFM is a key player in the development of innovative therapies for rare diseases, in particular muscular dystrophies.
