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A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis 期刊论文

编号：

f380827e-c233-4217-aa29-3ed1520c5ca4
作者：

Yang, Tong^[1] Wang, Zheng^[1] Wu, Fang^[1] Tan, Jingwei^[1] Shen, Yijun^[1] Li, Erguang^[2] Dai, Jingzhi^[3] Shen, Ronghai^[3] Li, Gang^[1] Wu, Jinsong^[1] Wang, Luochun^[1] Wang, Haibo^[1] Liu, Yanjun^[1,4]
语种：

英文
期刊：

PLOS COMPUTATIONAL BIOLOGY ISSN：1553-7358 2010 年 6 卷 2 期 ; FEB
收录：
摘要：

Etanercept, a TNF receptor 2-Fc fusion protein, is currently being used for the treatment of rheumatoid arthritis (RA). However, 25% to 38% of patients show no response which is suspected to be partially due to insufficient affinity of this protein to TNF alpha. By using computational protein design, we found that residue W89 and E92 of TNFR2 were critical for ligand binding. Among several mutants tested, W89Y/E92N displayed 1.49-fold higher neutralizing activity to TNFa, as compared to that of Etanercept. Surface plasmon resonance (SPR) based binding assay revealed that the equilibrium dissociation constant of W89Y/E92N to TNFa was 3.65-fold higher than that of Etanercept. In a rat model of collagen-induced arthritis (CIA), W89Y/E92N showed a significantly better ability than Etanercept in reducing paw swelling and improvement of arthritic joint histopathologically. These data demonstrate that W89Y/E92N is potentially a better candidate with improved efficacy in treating RA and other autoimmune diseases.
推荐引用方式
GB/T 7714：

Yang Tong,Wang Zheng,Wu Fang, et al. A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis [J].PLOS COMPUTATIONAL BIOLOGY,2010,6(2).
APA：

Yang Tong,Wang Zheng,Wu Fang,Tan Jingwei,&Liu Yanjun.(2010).A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis .PLOS COMPUTATIONAL BIOLOGY,6(2).
MLA：

Yang Tong, et al. "A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis" .PLOS COMPUTATIONAL BIOLOGY 6,2(2010).

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