Apolipoprotein C-III (APOC3) (APOC3)

Apolipoprotein C-III (APOC3) is a small glycoprotein primarily synthesized in the liver that plays a critical role in regulating plasma triglyceride levels (UniProt P02656). It is a component of triglyceride-rich lipoproteins (TRLs), including chylomicrons and very-low-density lipoproteins (VLDL), where it acts as a potent inhibitor of lipoprotein lipase (LPL) and hepatic lipase (PubMed: 24941081). Additionally, APOC3 impairs the hepatic clearance of TRL remnants by interfering with their interaction with the low-density lipoprotein (LDL) receptor and the LDL receptor-related protein 1 (LRP1). Genetic studies have consistently shown that loss-of-function mutations in the APOC3 gene are associated with lower triglyceride levels and a reduced risk of coronary heart disease (PubMed: 24941081). This has led to the development of several therapeutic modalities targeting APOC3, including antisense oligonucleotides like volanesorsen and olezarsen, as well as siRNA-based therapies like plozasiran (PubMed: 31163178, PubMed: 38446676). Furthermore, novel gene-editing technologies such as Verve-102 are now being explored to target the APOC3 genomic DNA locus directly, aiming to provide long-term suppression of the protein for patients with severe hypertriglyceridemia and familial chylomicronemia syndrome.

Other names

Apo-CIIIApolipoprotein C3APOC-IIIApolipoprotein C-III genomic DNA locus

Inhibition of APOC3 protein synthesis through mRNA degradation using antisense oligonucleotides and siRNA, or permanent disruption of the APOC3 genomic DNA locus using gene-editing technologies.