Angiopoietin-Like 3: From Discovery to Therapeutic Gene Editing

Xiao Wang; Kiran Musunuru

doi:10.1016/j.jacbts.2019.05.008

Angiopoietin-Like 3: From Discovery to Therapeutic Gene Editing

JACC Basic Transl Sci. 2019 Oct 28;4(6):755-762. doi: 10.1016/j.jacbts.2019.05.008. eCollection 2019 Oct.

Authors

Xiao Wang¹, Kiran Musunuru¹

Affiliation

¹ Department of Medicine and Department of Genetics, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

Hyperlipidemia is a major causal risk factor for atherosclerosis and coronary heart disease (CHD). Angiopoietin-like 3 (ANGPTL3) has emerged as a promising molecular target to reduce CHD risk due to its regulation of all 3 major lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Here, the authors review the discovery of ANGPTL3, the role of ANGPTL3 in lipoprotein metabolism, and the genetic association between naturally occurring ANGPTL3 loss-of-function mutations and CHD. In light of the favorable consequences of ANGPTL3 deficiency, various therapeutic strategies to target ANGPTL3 are currently in development, including a monoclonal antibody, an antisense oligonucleotide, and gene editing.

Keywords: ANGPTL3, angiopoietin-like 3; ASO, antisense oligonucleotide; CHD, coronary heart disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9; coronary artery disease; genetics; hoFH, homozygous familial hypercholesterolemia; lipids.

Publication types

Review