Apolipoprotein C-III (APOC3)

Class

siRNA (RNA interference) targeting hepatic APOC3 mRNA

Pathway

Lowers ApoC3 to reduce triglyceride-rich lipoprotein levels via LPL-independent and LPL-dependent clearance

Apolipoprotein C-III (ApoC3) is a small protein made mainly in the liver and carried on triglyceride-rich lipoproteins, including very-low-density lipoprotein (VLDL) and chylomicrons. It normally restrains the clearance of these particles from the bloodstream, both by inhibiting lipoprotein lipase (LPL), the enzyme that breaks down triglycerides within these particles, and through LPL-independent effects on receptor-mediated uptake by the liver. Elevated ApoC3 is associated with higher circulating triglyceride levels and has been linked epidemiologically to increased cardiovascular risk, while people with naturally low ApoC3 tend to have lower triglycerides and reduced cardiovascular event rates. This has made ApoC3 an attractive target for lowering triglycerides, particularly in patients with severe hypertriglyceridemia, including rare genetic forms of chylomicronemia where triglycerides can reach dangerously high levels and cause pancreatitis. Small interfering RNA (siRNA) approaches silence the messenger RNA (mRNA) that encodes ApoC3 inside liver cells, reducing production of the protein at its source rather than blocking it after secretion. This mechanism matters broadly across metabolic and cardiovascular disease contexts where triglyceride-rich lipoproteins contribute to risk, offering a route to sustained triglyceride reduction through a pathway distinct from statins or other lipid-lowering approaches.