Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases

Extending editing of mitochondrial DNA

30 September 2022

The number of mitochondrial genetic diseases that can be probed using DNA editing has been quadrupled thanks to a method that can switch adenine bases in human mitochondrial DNA to guanine ones.

Mutations in the DNA of mitochondria — the organelles that power cells — give rise to genetic diseases that afflict at least one person in 5,000. They can also cause age-related disorders such as diabetes and cancer.

Editing of mitochondrial DNA would allow researchers to gain more insights into mitochondrial genetic disorders, and it may eventually provide a way to treat them. But current editing methods can only swap a cytosine base with a thymine one.

Now, eight researchers from the Institute for Basic Science in South Korea have devised a way to convert an adenine base into a guanine one in human mitochondrial DNA.

This raises the proportion of pathogenic mutations involving a single base pair in mitochondrial DNA that can be edited from 10% to over 40%.

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References

1. Cell 185, 1764–1776 (2022). doi: 10.1016/j.cell.2022.03.039