Apolipoprotein B messenger RNA (APOB mRNA)

Apolipoprotein B (APOB) messenger RNA is the genetic template responsible for the synthesis of Apolipoprotein B-100, the primary structural protein found in pro-atherogenic lipoproteins such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). In the liver, APOB mRNA is translated into the protein required for the assembly and secretion of these lipid-carrying particles into the bloodstream. Elevated levels of APOB-containing lipoproteins are a major driver of atherosclerosis and cardiovascular disease, particularly in patients with genetic conditions like homozygous familial hypercholesterolemia (HoFH). Therapeutic targeting of APOB mRNA, primarily through antisense oligonucleotides like mipomersen, involves binding to the mRNA sequence to trigger its degradation by RNase H. This prevents the production of the APOB protein at the source, thereby significantly reducing circulating LDL cholesterol levels. While effective in lowering lipid profiles, pharmacological inhibition of this target is associated with risks of hepatic fat accumulation and liver enzyme elevations due to the inhibition of VLDL export from the liver.

Other names

ApoB mRNAApolipoprotein B-100 mRNAAPOB transcript

Antisense oligonucleotide-mediated RNase H-dependent degradation of mRNA to prevent translation of Apolipoprotein B-100 protein.