人干扰素α2b及IgG Fc片段融合蛋白显著延长体内半衰期.pdfVIP

生 物 工 程 学 报 Chin J Biotech 2008, January 25; 24(1): 53-62 journals.im.ac.cn Chinese Journal of Biotechnology ISSN 1000-3061 cjb@im.ac.cn ©2008 Institute of Microbiology, CAS CSM, All rights reserved. 研究报告 α2b IgG Fc 王 磊, 何 剑, 肖卫华 , , 230027 : 重组人干扰素α(rHuIFNα) 已被广泛用于临床治疗多种人类病毒性疾病和肿瘤。但IFNα在体内半衰期较短从而 导致IFNα在用药后数小时即从血浆中被清除。目前常用化学修饰和构建融合蛋白的方法来延长 IFNα 的半衰期。在本 研究中, 构建了 IFNα2b 与人 IgG 免疫球蛋白 Fc 片段的融合基因(IFNα2b-Fcγ)并在毕赤酵母中以二聚体形式分泌表达, 并有部分糖基化。不同亚型Fcγ 片段的融合蛋白对IFNα2b 抗病毒活性均有一定影响。其中IFNα2b-Fcγ2 所受影响最小, 较单纯的IFNα2b 降低了2.3 倍, 抗病毒活性可达4.29x107 IU/mg, 大鼠皮下注射后循环血液中半衰期达65 h, 血液中存 留时间 120 h 以上, 比商品重组干扰素的体内半衰期延长约 8 倍, 血液存留时间延长 10 倍, 显示了其良好的临床应用 前景。 : 干扰素 α2b, 免疫球蛋白, 融合蛋白, 半衰期, 毕赤酵母 Enhanced Circulation Half-life for Human IFNα2b and IgG Fc Fusion Protein Lei Wang, Jian He, and Weihua Xiao Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science Technology of China, Hefei 230027, China Abstract: Recombinant human interferon alpha (rHuIFNα) has been successfully used in antiviral and antitumor treatment. How- ever, it degrades rapidly in vivo, resulting in the disappearance of cytokine in the plasma within several hours after administration. Strategies including chemical modification and fusion proteins have been used to improve the half-life of IFNαin vivo. In the present study, we constructed fusion proteins with IFNα2b and the IgG Fc region from various subtypes of human IgG and expressed them in methylotropic yeast, Pichia pastries. The fusion proteins were secreted to the culture medium