Editing of mtDNA may correct genetic disorder

December 13, 2018 0 By FM

Payam A. Gammage et al reported the first in vivo successes in using zinc finger nucleases (ZFN) for selectively editing away pathogenic mitochondrial DNA (mtDNAs) in a heteroplasmic mammalian mitochondrial population. They demonstrated the correction of a cardiac-specific mitochondrial disorder with the concomitant therapeutic restoration of molecular and biochemical hallmarks to an undiseased state by exploiting a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue. Each of the two ZFN proteins used was systemically delivered to the mouse via a cardiotropic version of the adenovirus. The research offers a potential therapeutic route for treatment of heteroplasmic mitochondrial disease using programmable nucleases, where amelioration or halting of disease progression could be expected. Though the development has the potential to transform the prospects of many patients with mitochondrial disease, the researchers suggest for further work to be executed to enable the translation of these tools into effective medicines.

Nature Medicine (2018)/ https://www.nature.com/articles/s41591-018-0165-9 /24 September 2018