By Anthony Han
Mitochondria in almost all of our cells today first fused with other cells over a billion years ago, carrying their own double-stranded set of DNA, ribosomes, and proteins with them. Since then, their own baggage has largely been unaffected by evolution and unmodified by humans aside from replacing the mitochondria as a whole with one from a donor in the controversial “three-parent baby” process. Other editors, the most famous of which is CRISPR, were limited to DNA in our nuclei, whereas mutations within mitochondrial DNA would be unreachable. The ability to finely edit mitochondrial DNA comes from a surprising place; bacterial toxins.
The bacterium Burkholderia Cenocepacia produces a toxin that kills bacteria by editing DNA, swapping cytosine base pairs (C) to thymine (T). The most important detail is that this toxin, unlike all others, was able to edit double-stranded DNA rather than single-stranded DNA. This is far more efficient than those used previously, which involved prying apart the two strands, editing them separately, and stitching them back together.
By splitting the protein into two halves, the scientists were able to prevent the toxin from killing the cell immediately, although that would make it impossible to edit any DNA. However, by attaching DNA recognition proteins, they were able to reassemble the protein and edit the DNA at the correct position. Although the conversion is still inefficient, there is still work to be done.
This new discovery, when perfected, can improve the lives of many thousands of individuals. In the US, 1 in every 4,000 babies is affected by a disease carried on mitochondrial DNA. These diseases include mitochondrial myopathy, a disease-causing weak or nonfunctional muscles, Leber’s hereditary optic neuropathy, which causes progressive vision loss, and certain types of diabetes.
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