PCSK9/APOC3

Class

Dual PCSK9+APOC3 siRNA

PCSK9 and APOC3 are two proteins that the liver uses to control levels of fat-carrying particles in the blood. PCSK9 normally shortens the life of the LDL receptor, the docking site hepatocytes use to pull low-density lipoprotein (LDL) cholesterol out of circulation; less PCSK9 means more receptors available, and lower LDL cholesterol. APOC3 coats triglyceride-rich particles such as VLDL and chylomicrons and blocks the enzyme that breaks them down, so reducing APOC3 allows these particles to be cleared faster, lowering triglyceride levels. Both LDL cholesterol and triglyceride-rich remnant particles are independent, well-established contributors to atherosclerotic cardiovascular disease. A therapy that suppresses production of both proteins at once, rather than targeting either alone, is designed to correct mixed lipid abnormalities in a single treatment, which may be relevant for people whose cardiovascular risk is driven by both elevated LDL cholesterol and elevated triglycerides. This particular approach uses small interfering RNA (siRNA), a technology that degrades the messenger RNA instructions for a target protein before it can be made, rather than blocking the protein after it is produced. This mechanism is broadly relevant to atherosclerotic cardiovascular disease and to inherited or acquired disorders of lipid metabolism.