UCL Division of Biosciences


A novel strategy for ex vivo gene therapy using artificial chromosomes in human muscle stem cells published by CDB's Francesco Saverio Tedesco and colleagues in EMBO Molecular Medicine

18 December 2017

In this new study Sara Benedetti et al.

have shown that reversible immortalisation of human dystrophic muscle progenitor cells enables their genetic correction with novel human artificial chromosomes (HACs) containing the entire dystrophin genetic locus, providing evidence of translation of HAC technology for ex vivo gene therapy of Duchenne muscular dystrophy. The authors have first used lentiviral vectors to deliver specific genes to extend proliferation of different types of human skeletal muscle progenitor cells. Importantly, they have also made this process reversible. The extension of the proliferative ability of muscle cells derived from patients with Duchenne muscular dystrophy allowed their genetic correction with a novel HAC. Finally, this strategy enabled the development of a next‐generation, multifunctional HAC containing several different genes, which could be one of the largest and most complex gene therapy vectors developed to date. This exciting study has been developed in collaboration with scientists at the University of Manchester, University of Milan (Italy) and Tottori University (Japan).

Read full paper: Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next‐generation human artificial chromosomes for Duchenne muscular dystrophy

Authors: Sara Benedetti, Narumi Uno, Hidetoshi Hoshiya, Martina Ragazzi, Giulia Ferrari, Yasuhiro Kazuki, Louise Anne Moyle, Rossana Tonlorenzi, Angelo Lombardo, Soraya Chaouch, Vincent Mouly, Marc Moore, Linda Popplewell, Kanako Kazuki, Motonobu Katoh, Luigi Naldini, George Dickson, Graziella Messina, Mitsuo Oshimura, Giulio Cossu, Francesco Saverio Tedesco