MELAS: a precision endonuclease to reverse the ratio of mutated to normal mitochondrial DNA

ARCUS endonucleases developed by Precisions BioSciences (Durham, United States) are, unlike ZNF or TALENS nucleases, unique protein components, which means they can be integrated into AAV9. The mitoARCUS endonuclease has been specifically developed to eliminate the m.3243A>G mitochondrial DNAmacromolécule complexe, l’ADN est le support de l’hérédité (gènes). C’est le constituant des chromosomes. L’ADN est organisé en double hélice (deux brins complémentaires) et constitué de nucléotides de quatre types : adénine, guanine, cytosine et thymine. mutations responsible for more than 80% of MELAS syndromes.

When tested on a cell line and on a tumour transplanted into a mouse, the mitoARCUS endonuclease proved effective in reversing heteroplasmy in favour of normal mitochondrial DNA and improving mitochondrial function, without off-target nuclear modification.

Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease. Shoop WK, Lape J, Trum M et al. Nat Metab. 2023 Dec;5(12):2169-2183.