Transcriptomic therapy for dyslipidemias utilizing nucleic acids targeted at ANGPTL3

Gerald F. Watts, Frederick J. Raal, Dick C. Chan

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)


Angiopoietin-like protein 3 (ANGPTL3) is a key physiological regulator of plasma lipid and lipoprotein metabolism that involves the control of enzymes, lipoprotein and endothelial lipases. Inhibition of ANGPTL3 offers a new approach for correcting the health risks of dyslipidemia, including familial hypercholesterolemia, mixed hyperlipidemia, metabolic syndrome and/or severe hypertriglyceridemia. ANGPTL3 inhibition with nucleic acid-based antisense oligonucleotide and siRNA can correct dyslipidemia chiefly by reducing production and increasing catabolism of triglyceride-rich lipoprotein and LDL particles. Early clinical trials have demonstrated that these agents can safely and effectively lower plasma triglyceride and LDL-cholesterol levels by up to 70 and 50%, respectively. However, the long-term safety and cost-effectiveness of these agents await to be confirmed in an ongoing and future clinical trials.

Lay abstract Angiopoietin-like protein 3 (ANGPTL3) is a protein that is produced by the liver. ANGPTL3 plays an important role in controlling the blood levels of fats, such as cholesterol. Inhibition of ANGPTL3 is a new approach to improve the health in people with abnormal blood fat levels. Treatments that inhibits ANGPTL3, such as nucleic acids that reduce products of genes called RNA, can safely and significantly lower blood fat levels. The safety and value of this new treatment in preventing heart disease in people needs further research.

Original languageEnglish
Pages (from-to)143-153
Number of pages11
JournalFuture Cardiology
Issue number2
Publication statusPublished - Feb 2022


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