Silencing the Bad Cholesterol Gene

Durable and efficient gene silencing in vivo by hit-and-run epigenome editing
“[We, at San Raffaele Telethon Institute for Gene Therapy, Milan, Italy] targeted Pcsk9, a gene expressed in hepatocytes that is involved in cholesterol homeostasis. In vitro screening of different editor designs indicated that zinc-finger proteins were the best-performing DNA-binding platform for efficient silencing of mouse Pcsk9. A single administration of lipid nanoparticles loaded with the editors’ mRNAs almost halved the circulating levels of PCSK9 for nearly one year in mice. Notably, Pcsk9 silencing and accompanying epigenetic repressive marks also persisted after forced liver regeneration, further corroborating the heritability of the newly installed epigenetic state.” MORE
Image Credit: Phys.org