癌睾新分子BAP31特异性核酸适配体的筛选及其功能研究

项目名称： 癌睾新分子BAP31特异性核酸适配体的筛选及其功能研究

项目编号： No.31500614

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 陶亮

作者单位： 中国人民解放军第四军医大学

项目金额： 20万元

中文摘要： 肿瘤早期诊断与靶向治疗是肿瘤研究的热点。但是由于肿瘤的多种逃逸机制使得以肿瘤相关抗原作为早期诊断与治疗靶点效果并不理想。我们课题组通过前期研究发现BAP31是一种新的肿瘤/睾丸抗原（CT抗原），提示其可以作为肿瘤特异性抗原成为诊断与治疗的潜在靶点。核酸适配体特异性高、亲和力强、免疫原性小等特点，使其在肿瘤诊断与治疗方面能更好的达到特异性好、敏感性高、机体排异反应小、对人体几乎无毒等要求，从而极具优势。本项目拟采用我课题组已证明可作为潜在肿瘤诊疗靶点的CT抗原BAP31为靶分子，将指数富集配体系统进化技术、磁分离技术、流式细胞术相结合，从随机文库中筛选出可与BAP31特异结合的核酸适配体分子。再通过对核酸适配体分子进行功能化修饰，从细胞、组织和动物体内三方面鉴定BAP31特异性适配体在相对复杂环境下的结合能力，为后续建立基于BAP31特异性核酸适配体的肿瘤诊断与靶向治疗奠定基础。

中文关键词： 核酸；蛋白质；亲和常数；B细胞受体相关蛋白；适配体

英文摘要： Early diagnosis and targeted therapy of tumor are the hot spots in the tumor research. Because of various tumor escape mechanisms, the tumor associated antigens as early diagnosis and therapeutic targets in effect are not ideal. The previous studies of our research group found that BAP31 is a novel cancer/testis antigen (CT antigen), which suggest that it will be a tumor specific antigen as potential target for diagnosis and therapy. Aptamers have a great advantage in diagnosis and treatment of tumor because of their characteristics, such as high specificity, strong affinity, low immunogenicity and so on. These characteristics make them better to meet the specificity, sensitivity, rejection, low-toxic requirements. This project aims to adopt BAP31 as target for aptamers' selection. Combining with the SELEX, magnetic enrichment technology and flow cytometry, the aptamers will be selected from random nucleic acid libraries. Furthermore, the functionalization of aptamers will be tested and verified in three aspects of cells, tissues and animal bodies for specific binding capacity in the relatively complex environments, which will establish the basis of the diagnosis and treatment tumor using BAP31's aptamers.

英文关键词： nucleic acid;protein;affinity constant;B cell receptor associated protein;aptamer