Another CRISPR step in the way out of congenital muscular dystrophy type 1A (MDC1A) is announced by Ronald Cohn and colleagues in Nature this week. This is still preclinical research in mice, but the indirect approach presented by the Canadian team holds great promise.
Given the high number of MDC1A-causing alterations, standard genetic correction using CRISPR would require the design of multiple RNA guides specific to each mutation. By contrast, the attenuation of disease pathogenicity by targeted modulation of the expression of disease-modifier genes could be safer and would benefit all patients. The researchers from the Hospital for Sick Children in Toronto are hopeful their strategy will prove versatile, as they write in the paper’s final paragraph.
“An application as a combinatorial therapeutic approach, involving concurrent upregulation of protective disease-modifier genes and downregulation of detrimental genes, would represent a new paradigm for lessening disease phenotypes. In summary, our study establishes a framework to use CRISPR–Cas9 to modulate gene expression of disease modifiers that should be considered as a mutation-independent therapeutic strategy not only to treat MDC1A, but also for the treatment of various other inherited and acquired diseases”.