APOC3

Class

APOC3 siRNA

Apolipoprotein C-III (APOC3) is a small protein made mainly in the liver and carried on triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoprotein (VLDL). It acts as a natural brake on the clearance of these particles: it inhibits lipoprotein lipase, the enzyme that breaks down triglycerides in the bloodstream, and interferes with receptor-mediated uptake of lipoprotein remnants by the liver. Because of this, higher APOC3 levels are associated with higher circulating triglycerides, while genetic loss of APOC3 function is associated with low triglycerides and reduced cardiovascular risk. This has made APOC3 an attractive target for lowering severely elevated triglycerides, particularly in familial chylomicronemia syndrome, where triglyceride accumulation can cause recurrent, dangerous pancreatitis, and more broadly in hypertriglyceridemia linked to cardiovascular disease. Therapeutic strategies aim to reduce the amount of APOC3 protein produced or block its activity, thereby removing the brake on triglyceride clearance and restoring more normal lipid handling. Approaches under investigation include RNA-targeting molecules that reduce hepatic APOC3 production, gene-editing approaches intended to permanently silence the gene, and small molecules that may modulate its function directly. Across these approaches, the shared rationale is the same: lowering APOC3 activity to improve clearance of triglyceride-rich lipoproteins.