蛋白质工程手段修饰干扰素的实际应用研究进展  

Progress of Modifying Interferon by Protein Engineering

作　　者：程天翼[1] 靳维维[1] 高向东[1] 顾觉奋[1] 

机构地区：[1]中国药科大学生命科学与技术学院,南京210009

出　　处：《国外医药（抗生素分册）》2011年第4期156-160,共5页World Notes on Antibiotics

摘　　要：干扰素是一类具有抗病毒、抗增殖、免疫调节等生物学功能的细胞因子,也是临床上抗病毒抗肿瘤的常用药。但是,干扰素不稳定、半衰期短等缺点限制了它的应用。近年来,一系列蛋白质工程手段被用于修饰干扰素并取得了良好的结果。针对延长半衰期,聚乙二醇修饰、糖蛋白修饰、白蛋白修饰、人lgG免疫球蛋白Fc片段融合被证明有效,而去唾液酸糖蛋白受体介导的靶向修饰、人源化抗HBs抗体基因融合及肿瘤靶向病毒载体的构建也为干扰素靶向修饰提供了新的选择。现对蛋白质工程手段在修饰干扰素方面的实际应用做一概述。Interferons is a family of cytokines which exert a multiplicity of biological actions including antiviral, antiproliferative, immunomodulatory effects and It is therefore also widely used in clinical practice to treat a variety of viral diseases and cancers. However, its disadvantages such as instability, short circulating half-life limit its application. In recent years, to circumvent this problem, a series of protein engineering strategies have been carried out carried out to modify interferons and remarkable results have been achieved. PEGylation, glycosylation, albumin fusion and lgG Fc fusion has proved effective to prolong its half-life, while conditions for targeted anticancer therapy have been prepared by asialoglycoprotein receptor-mediated targeted modification, human anti-HBs dsFv-IFN fusion gene technology and construction of tumor-targeting virus vector. Herein the latest research methods of interferon modulations via protein engineering were reviewed.

关 键 词：干扰素 定点突变 基因融合 半衰期 靶向药物 

分 类 号：R978.7[医药卫生—药品]