Hepatic delivery of miroRNA-30c analog reduces plasma cholestrol in mice and monkeys and atherosclerosis in mice without causing liver injury

High plasma cholesterol levels contribute substantially to this problem. Here, we show that hepatic delivery of a microRNA-30c analog C2 reduces plasma cholesterol levels in apoB-containing lipoproteins in hypercholesterolemic C57Bl6 mice, and in African green monkeys that spontaneously developed diabetes and hyperlipidemia.

In addition, it prevented diet-induced hypercholesterolemia in FRG-mice with humanized livers. Furthermore, C2 significantly reduced plasma cholesterol and atherosclerosis in LDL receptor knockout mice indicating that the cholesterol-lowering effects of C2 do not rely on the presence of LDL receptors. In all these studies, C2 had no effect on hepatic triglyceride and cholesterol, plasma ALT, AST, CK-MB, ALP, IL-6, TNF-α, and INF-ϒ indicating absence of tissue lipid accumulation, inflammatory and immune responses.