Apolipoprotein B gene (APOB)

The Apolipoprotein B (APOB) gene provides the genetic instructions for producing two essential isoforms of the apolipoprotein B protein: ApoB-48 and ApoB-100 [NCBI Gene ID: 338]. These proteins serve as the primary structural scaffolds for pro-atherogenic lipoproteins, including chylomicrons, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) [UniProt: P04114]. Elevated levels of ApoB-containing particles are a major driver of cholesterol deposition in arterial walls, leading to atherosclerosis and coronary artery disease [PubMed: 31611126]. While traditional therapies like statins or antisense oligonucleotides target the protein or mRNA, the APOB genomic DNA sequence is now a target for permanent therapeutic intervention via gene editing [Verve Therapeutics]. Investigational therapies like VERVE-201 utilize base editing technology to introduce precise changes in the APOB DNA sequence within hepatocytes to durably silence the gene [Nature Communications: 13, 2022]. This approach aims to provide a one-time treatment to significantly lower LDL cholesterol and reduce the lifelong risk of cardiovascular events, particularly in patients with refractory hypercholesterolemia.

Other names

APOBApolipoprotein B-100 geneApolipoprotein B-48 geneFLDBLDLCQ4Apolipoprotein B genomic DNA

Permanent gene silencing via CRISPR-mediated base editing to disrupt the production of the Apolipoprotein B protein in the liver.