Therapeutic prospects for CRISPR genome editing

21 August 2014

A new paper in Science reports on the successful use of genome editing to counteract the disease Duchenne muscular dystrophy in a mouse model.

The CRISPR/Cas9–mediated genome editing technique first published in 2013 was immediately hailed as a potentially highly valuable new tool for applications including gene therapy for disease.

Duchenne muscular dystrophy (DMD)  is an inherited X-linked disease caused by mutations in the dystrophin (DMD) gene. The condition causes progressive muscle weakness and early death, and in most cases has no treatment, although the first therapeutic for use in patients with a nonsense DMD mutation received EU approval earlier this year.

Now US researchers have used the CRISPR technique on mdx mice with a germline mutation in the mouse dystrophin gene (Dmd), an effective mouse model of DMD. This resulted in mosaicism, animals having a variable degree of gene correction (successful introduction of and expression from the healthy version of the Dmd gene) in their cells, from 2-100%.

However, despite this variability the phenotypic rescue of the DMD phenotype in these mice was higher, i.e. despite having only very low correction of the dystrophin gene in some cells, the mice showed a greater than expected degree of protection from DMD symptoms. The speculate that this may be due to the recruitment of successfully corrected muscle cells to help create functional muscle fibres, and conclude that ‘this strategy may one day allow correction of disease-causing mutations in the muscle tissue of patients with DMD’.

The scientists note several caveats to their work, not least the obvious differences between mice and humans and the challenges of moving from germline to somatic cell gene editing. As with any form of gene therapy, effective delivery to the target muscle cells is also a barrier. However, as a proof-of-principle it is a promising sign for the clinical application of genome editing in the treatment of serious inherited diseases.

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