Chorba Lab

Research focus

NIH R01 · 2024

Chemical Biology to Modulate PCSK9 and Treat Atherosclerosis

PROJECT SUMMARY/ABSTRACT Serum low-density lipoprotein (LDL) causes atherosclerotic heart disease. As the LDL receptor (LDLR) on the liver clears LDL from the blood, upregulating hepatic LDLR reduces both LDL and cardiovascular events. The self-cleaving protease PCSK9 (proprotein convertase subtilisin/kexin type 9) is a validated therapeutic target; it chaperones the LDLR for lysosomal degradation, downregulating its function. Antibodies against PCSK9 lower LDL and improve clinical outcomes, but cost and administration requirements illustrate a need for alternatives. Liver-targeted siRNA also robustly lowers LDL, but unlike the well-tolerated genetic variants, it removes all PCSK9 from the…

From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.