Epigenome Editing for Lipid Reduction and Atherosclerosis Inhibition: A New Therapeutic Paradigm
Hypercholesterolemia Threatens Heart Disease
This study illuminates hypercholesterolemia, the root cause of atherosclerotic cardiovascular disease, the leading cause of death worldwide. Existing drugs achieve only transient reductions in blood lipids, making long‑term management difficult.
Epigenome Editing Permanently Targets Hepatocytes
The CRISPRoff system was delivered via AAV and lipid nanoparticles to the liver to epigenetically suppress the Hmgcr or Pcsk9 genes. Without altering the DNA sequence, gene expression is continuously blocked.
Future Significance and Outlook
Hypercholesterolemia‑driven cardiovascular disease is a realistic problem that is difficult to treat and manage. A one‑time therapy that lowers blood lipids could provide substantial health benefits in daily life.
Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies substantially improve circulating lipid profiles, strategies that provide more durable, safe, and efficient control of lipid metabolism are still needed. Epigenome editing offers a promising approach for long-lasting repression of disease-modifying genes without altering the underlying DNA sequence. Here, we develop CRISPRoff platforms delivered by adeno-associated virus or lipid nanoparticle to epigenetically silence hepatic Hmgcr or Pcsk9 in vivo. In both C57BL/6J wild-type and ApoE
Hypercholesterolemia‑driven cardiovascular disease is a realistic problem that is difficult to treat and manage. A one‑time therapy that lowers blood lipids could provide substantial health benefits in daily life.