Apolipoprotein C3 (APOC3) gene adenine (APOC3)

The target refers to a specific adenine nucleotide within the Apolipoprotein C3 (APOC3) gene that is accessible for modification by adenine base editors (ABEs) (Gaudelli et al., 2017). APOC3 is a key regulator of triglyceride metabolism, primarily synthesized in the liver, where it inhibits lipoprotein lipase (LPL) and the hepatic uptake of triglyceride-rich lipoproteins (UniProt P02658). Elevated levels of APOC3 are a known risk factor for hypertriglyceridemia and coronary artery disease, while loss-of-function mutations are associated with lower triglyceride levels and cardiovascular protection (Pollin et al., 2008). By utilizing a CRISPR-Cas9 system to create a single-stranded DNA editing window, an ABE can deaminate a target adenine to inosine, which is subsequently repaired as guanine. This precise A-to-G transition can be used to knock out the gene by disrupting the start codon or altering splice sites, offering a potential one-and-done therapeutic approach for severe lipid disorders (Musunuru, 2023). Experimental therapies targeting this site aim to significantly reduce APOC3 protein expression and plasma triglyceride concentrations in patients with conditions like familial chylomicronemia syndrome.

Other names

APOC3 gene adenineApolipoprotein C-III gene adenineAPOC3 editing siteAPOC3 ABE targetAdenine within the APOC3 editing window

Targeted deamination of adenine to inosine within the genomic DNA, resulting in a permanent A-to-G transition during DNA replication or repair