Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9. (https://pubmed.ncbi.nlm.nih.gov/38781968/)
These scientists wanted to find a way to make a special enzyme called GeoCas9 more effective at editing genes in human cells. They found that the original GeoCas9 enzyme was not very good at editing genes in human cells. So, they worked in the lab to change the GeoCas9 enzyme and make it better at editing genes.
They used a technique called cryo-electron microscopy to look at the structure of the original GeoCas9 enzyme and the improved version they created, called iGeoCas9. They found that the iGeoCas9 enzyme had more connections with the DNA it was trying to edit.
By studying how the iGeoCas9 enzyme works, they discovered that it is better at unwinding the DNA to make it easier to edit. This is important because human cells have different conditions than the bacteria where the original GeoCas9 enzyme worked best.
The scientists also learned that by improving the GeoCas9 enzyme, they could use the same strategy to make other similar enzymes better at editing genes. This study showed that by understanding how these enzymes work, scientists can make them more effective at changing genes, which is very important for genetic research and medicine.
Eggers AR., Chen K., Soczek KM., Tuck OT., Doherty EE., Xu B., Trinidad MI., Thornton BW., Yoon PH., Doudna JA. Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9. Cell. 2024 May 13:S0092-8674(24)00457-4. doi: 10.1016/j.cell.2024.04.031.