A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease

• DOI: 10.1186/s12951-022-01456-z
• Publication Date: 2022-05-19T09:07:04Z
• Authors: Xiaozhi Hu; Jiajun Fan; Qianqian Ma; Lei Han; Zhonglian Cao; Caili Xu; Jingyun Luan; Guangjun Jing; Yanyang Nan; Tao Wu; Yuting Zhang; Hanqi Wang; Yuanzhen Zhang; Dianwen Ju
• Keywords: 0303 health sciences; Research; Hypercholesterolemia; Cholesterol, LDL; Lipids; Lipid-reducing; 3. Good health; Mice; 03 medical and health sciences; Angiopoietin-like Proteins; ANGPTL3; Non-alcoholic Fatty Liver Disease; NAFLD; Nanobody; Medical technology; Animals; R855-855.5; TP248.13-248.65; Triglycerides; Biotechnology; Angiopoietin-Like Protein 3

Nonalcoholic fatty liver disease (NAFLD) is a metabolic mainly on account of hypercholesterolemia and may progress to cirrhosis hepatocellular carcinoma. The discovery effective therapy for NAFLD an essential unmet need. Angiopoietin-like protein 3 (ANGPTL3), critical lipid metabolism regulator, resulted in increased blood lipids was elevated NAFLD. Here, we developed nanobody-heavy chain antibody (VHH-Fc) inhibit ANGPTL3 treatment.In this study, retrieved anti-ANGPTL3 VHH Fc fusion protein, C44-Fc, which exhibited high affinities proteins rescued ANGPLT3-mediated inhibition lipoprotein lipase (LPL) activity. C44-Fc bound distinctive epitope within when compared with the approved evinacumab, showed higher expression yield. Meanwhile, had significant reduction triglyceride (~ 44.2%), total cholesterol 36.6%) LDL-cholesterol 54.4%) hypercholesterolemic mice ameliorated hepatic accumulation injury model.We discovered VHH-Fc affinity ANGPTL3, strong stability also alleviated progression NAFLD, might offer promising