REVIEW: Genome- and Cell-Based Strategies in Therapy of Muscular Dystrophies

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Y. Bou Saada^1#, Carla Dib^1#, M. Lipinski¹, and Y. S. Vassetzky^1,2*

¹UMR 8126, CNRS, Université Paris-Sud, Université Paris Saclay, Institut de Cancérologie Gustave-Roussy, F-94805 Villejuif, France; E-mail: vassetzky@igr.fr

²Lomonosov Moscow State University, 119991 Moscow, Russia

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received February 24, 2016; Revision received April 4, 2016

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Muscular dystrophies are a group of heterogeneous genetic disorders characterized by progressive loss of skeletal muscle mass. Depending on the muscular dystrophy, the muscle weakness varies in degree of severity. The majority of myopathies are due to genetic events leading to a loss of function of key genes involved in muscle function. Although there is until now no curative treatment to stop the progression of most myopathies, a significant number of experimental gene- and cell-based strategies and approaches have been and are being tested in vitro and in animal models, aiming to restore gene function. Genome editing using programmable endonucleases is a powerful tool for modifying target genome sequences and has been extensively used over the last decade to correct in vitro genetic defects of many single-gene diseases. By inducing double-strand breaks (DSBs), the engineered endonucleases specifically target chosen sequences. These DSBs are spontaneously repaired either by homologous recombination in the presence of a sequence template, or by nonhomologous-end joining error prone repair. In this review, we highlight recent developments and challenges for genome-editing based strategies that hold great promise for muscular dystrophies and regenerative medicine.

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KEY WORDS: muscular dystrophies, gene editing, cell therapy

DOI: 10.1134/S000629791607004X

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