التفاصيل البيبلوغرافية
| العنوان: |
Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells. |
| المؤلفون: |
Li, Xinyang, Zhang, Wei, Shu, Yu, Huo, Rui, Zheng, Chengyang, Qi, Qi, Fu, Pengfei, Sun, Jie, Wang, Yuhuan, Wang, Yan, Lu, Juxu, Zhao, Xiangjie, Yin, Guoyou, Wang, Qingqing, Hong, Jun |
| المصدر: |
Scientific Reports; 7/3/2024, Vol. 14 Issue 1, p1-11, 11p |
| مصطلحات موضوعية: |
LDL cholesterol, SURFACE plasmon resonance, IMMUNOGLOBULINS, LOW density lipoprotein receptors, ANTILIPEMIC agents, SUBTILISINS, LOW density lipoproteins |
| مستخلص: |
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 μM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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