Gene therapy: Gene-editing therapy for neurological disease

Moira A. McMahon & Don W. Cleveland. Nature Reviews Neurology 13, 7–9 (2017) doi:10.1038/nrneurol.2016.190 Published online 16 December 2016.

Guide RNA-mediated CRISPR–Cas nucleases are a powerful technology for the engineering of mammalian genomes. CRISPR–Cas9-dependent editing of mutated genes that cause Huntington disease and fragile X syndrome was recently achieved in cell-based models, heralding the first step towards developing this technology into viable therapeutics for neurological diseases.
The successful translation of these proof‑of‑principle studies to in vivo gene editing is eagerly anticipated, but several challenges remain. One major challenge is delivery of the sgRNA and nuclease to target cells. A final major challenge for extension of gene-editing approaches to applications within the nervous system is the efficiency of gene silencing or correction: can the changes be made in sufficient numbers of cells to alter the disease course?.
What seems certain is that continued development of genome-editing technology to target neurological diseases is likely to provide a greater understanding of the diseases themselves and, hopefully, will one day form the basis of a successful therapy.