Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors

Editing mitochondrial DNA more precisely

29 April 2023

A way to edit the DNA in mitochondria — the powerhouses of cells — with minimal off-target changes has been demonstrated.

Mitochondria contain small, circular rings of DNA. Mutations in this mitochondrial DNA can give rise to severe, uncurable diseases. Scientists are thus keen to develop ways to edit mitochondrial DNA.

A promising method involves using base editors derived from a bacterial toxin, but this introduces many off-target mutations.

Now, a team led by researchers from the Institute for Basic Science in South Korea has found a way to greatly enhance the accuracy of this method for editing mitochondrial DNA.

The bacterially derived editors consist off two parts, and they only become active when combined. By swapping alanine for amino-acid residues at the interface between the two halves, the team succeeded in greatly reducing off-target activity.

The researchers anticipate that their demonstration could lead to future therapies for mitochondrial genetic disorders.

Supported content

References

1. Nature Biotechnology 41, 378–386 (2023). doi: 10.1038/s41587-022-01486-w