Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA. (https://pubmed.ncbi.nlm.nih.gov/38181745/)

These scientists wanted to find a way to fix problems in our DNA that can cause diseases. They focused on a part of our DNA called mitochondrial DNA, which is responsible for giving our cells energy. They used two special tools called DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) to make changes to the mitochondrial DNA.

But they found that one of these tools, called A-to-G-editing TALEDs, was causing some unintended changes in the cells. It was changing not only the mitochondrial DNA but also the RNA, which is a molecule that helps make proteins in our cells. These unintended changes could cause problems in the cells and make the tool less effective.

So, the scientists decided to make changes to the A-to-G-editing TALEDs to reduce these unintended changes. They made the tool more precise so that it would only make the changes in the mitochondrial DNA that they wanted. They tested these new and improved tools in cells and also in mouse embryos.

The good news is that the new and improved tools worked much better! They didn't cause as many unintended changes in the cells, and they didn't harm the mouse embryos. In fact, they were able to create mice with a specific disease-causing mutation in their mitochondrial DNA. These mice showed a reduced heart rate, which is a symptom of the disease they were studying.

Overall, these scientists made important improvements to the tools they use to fix problems in our DNA. This will help them better understand and treat diseases caused by issues in mitochondrial DNA.

Cho SI., Lim K., Hong S., Lee J., Kim A., Lim CJ., Ryou S., Lee JM., Mok YG., Chung E., Kim S., Han S., Cho SM., Kim J., Kim EK., Nam KH., Oh Y., Choi M., An TH., Oh KJ., Lee S., Lee H., Kim JS. Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA. Cell. 2024 Jan 4;187(1):95-109.e26. doi: 10.1016/j.cell.2023.11.035.