与细胞因子特异结合的寡聚核苷酸适配子及其在诊断和治疗中的应用  

Cytokine Aptamers as Therapeutic and Diagnostic Agents

作　　者：严馨蕊[1] 高绪文[1] 张智清[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所病毒基因工程国家重点实验室,北京100052

出　　处：《生物工程学报》2004年第4期627-632,共6页Chinese Journal of Biotechnology

基　　金：国家高技术 863计划基金资助 (No.2 0 0 1AA2 15 2 5 1)~~

摘　　要：寡聚核苷酸适配子 (Aptamer)是用指数富集式配基系统进化方法 (SELEX )筛选出的寡聚核苷酸 ,它能与靶分子特异性结合 ,具有识别和抑制靶物质生物学活性的作用。将体外筛选到的寡聚核苷酸适配子作为在动物或人体内应用的药剂 ,还需要进行化学修饰来提高它的生物利用度和在血浆中的稳定性。 2 氟、2′ 烷氧基或 2′ 氨基修饰可以提高适配子的稳定性 ,使适配子的体外半衰期延长 ;5′端交联一个高分子量的PEG分子或脂质体分子 ,可以使它的血浆清除率由 1小时提高到几小时至 1天。修饰后仍保持生物学活性的适配子可用于治疗相应靶细胞因子引起的疾病。目前 ,国内外已经筛选到了十几种细胞因子的适配子 ,其中血管内皮生长因子已经用于临床疾病的治疗。除了用于临床治疗外 ,适配子还可以用于细胞因子的诊断 ,凡是涉及抗体的诊断领域 ,几乎都可以用寡聚核苷酸适配子代替。应用大规模机械化筛选技术 ,可以在短期内筛选到大量的高特异性、高亲和力适配子 。Aptamers are oligonucleotides derived from an in vitro evolution process called SELEX(Systematic Evolution of Ligands by Exponential Enrichment). Aptamers specially binding to targets could recognize and inhibit the function of targets. Using this method, many powerful antagonists of cytokines have been found. In order for these antagonists to work in animal models of disease and in humans, it is necessary to modify the aptamers. First of all, 2′ F, 2′ NH 2 and 2′ CH 3O modifications of nucleoside triphosphates could prolong half lives in blood. Aptamers can be kept in the circulation from hours to days by conjuga ting them to higher molecular weight vehicles. After modified, conjugated aptamers are injected into animals, they inhibit physiological functions known to be associated with their target cytokines. Exhibiting binding characteristics comparable to or even better than monoclonal antibodies, these ligands can be used as detection probes, highly efficient inhibitors of protein function or specific competitors in high throughput screening (HTS) assays. Recently several aptamers of cytokines have been characterized. Some of them have been used as diagnostic agent for the detection of target cytokines. The first aptamer that has proceeded to phaseⅡclinical studies is NX 1838, an injectable angiogenesis inhibitor that can be potentially used to treat macular degeneration induced blindness. Aptamers will be versatile tools that can greatly enhance the efficiency of modern diagnose and therapy development.

关 键 词：SELEX APTAMER 细胞因子 血管内皮生长因子 寡聚核苷酸 

分 类 号：R446.6[医药卫生—诊断学] R459.9[医药卫生—临床医学]