Durable and efficient gene silencing in vivo by hit-and-run epigenome editing. (https://pubmed.ncbi.nlm.nih.gov/38418872/)

These scientists wanted to find a way to treat human diseases by changing how certain genes work in our bodies. They focused on a gene called Pcsk9, which is important for controlling cholesterol levels in the liver. The scientists tested different tools to see which one could best turn off this gene in mice.

They found that a tool called zinc-finger proteins worked the best at switching off the Pcsk9 gene. They then put these tools into tiny particles called lipid nanoparticles, which they injected into the mice. This treatment almost cut the levels of the PCSK9 protein in the mice's blood in half for almost a year.

Even when the mice's livers were forced to grow back, the gene stayed switched off, showing that this change was passed down to new cells. The scientists then improved their tools to make a new design called evolved engineered transcriptional repressor (EvoETR), which was even better at turning off the gene without causing any damage to the DNA.

This study shows that it's possible to change how genes work in living animals without harming them, opening up new possibilities for treating diseases by controlling gene activity.

Cappelluti MA., Mollica Poeta V., Valsoni S., Quarato P., Merlin S., Merelli I., Lombardo A. Durable and efficient gene silencing in vivo by hit-and-run epigenome editing. Nature. 2024 Feb 28. doi: 10.1038/s41586-024-07087-8.