Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides

• Published in: The New England journal of medicine Vol. 377; no. 3; pp. 222 - 232
• Main Authors: Graham, Mark J, Lee, Richard G, Brandt, Teresa A, Tai, Li-Jung, Fu, Wuxia, Peralta, Raechel, Yu, Rosie, Hurh, Eunju, Paz, Erika, McEvoy, Bradley W, Baker, Brenda F, Pham, Nguyen C, Digenio, Andres, Hughes, Steven G, Geary, Richard S, Witztum, Joseph L, Crooke, Rosanne M, Tsimikas, Sotirios
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 20.07.2017
• Subjects: Adult; Aged; Angiopoietin; Angiopoietin-like Proteins; Angiopoietins - antagonists & inhibitors; Angiopoietins - genetics; Animals; Antisense oligonucleotides; Antisense RNA; Apolipoprotein B; Apolipoprotein C-III; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Atherosclerosis - prevention & control; Cholesterol; Coronary Artery Disease - genetics; Coronary Artery Disease - metabolism; Disease Models, Animal; Double-Blind Method; Drug dosages; Dyslipidemias - blood; Dyslipidemias - drug therapy; Female; Gene expression; Humans; Lipid Metabolism - drug effects; Lipids; Lipids - blood; Lipoproteins; Low density lipoprotein; Male; Mice; Mice, Inbred Strains; Middle Aged; mRNA; Oligonucleotides - pharmacology; Oligonucleotides - therapeutic use; Oligonucleotides, Antisense - pharmacology; Oligonucleotides, Antisense - therapeutic use; Pharmacodynamics; Plasma; RNA, Messenger - antagonists & inhibitors; Triglycerides
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1701329

Angiopoietin-like 3 (ANGPTL3) inhibits endothelial lipase and lipoprotein lipase. Injection of antisense oligonucleotides targeting ANGPTL3 messenger RNA effects a reduction of atherogenic lipoproteins in humans and mice and a slowing of progression of atherosclerosis in mice.