Selection of DNA aptamers against epidermal growth factor receptor with high affinity and specificity
Selection of DNA aptamers against epidermal growth factor receptor with high affinity and specificity
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高亲和力和特异性的针对表皮生长因子受体的DNA适体的筛选 高亲和力和特异性的针对表皮生长因子受体的DNA适体的筛选
DOI：
10.1016/j.bbrc.2014.09.023
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发表时间：
2014-10-31
影响因子：
3.1
通讯作者：
Kang, De-Zhi
中科院分区：
文献类型：
--
作者：
Wang, Deng-Liang;Song, Yan-Ling;Kang, De-Zhi
表皮生长因子受体（Epidermal growth factor receptor，EGFR/HER 1/c-ErbB 1）在表皮样癌、恶性胶质瘤等多种实体瘤中过表达，在恶性肿瘤细胞的增殖、侵袭、血管生成和转移中起重要作用，是临床肿瘤检测、显像和治疗的理想抗原。适体是通过指数富集系统进化配体（SELEX）的产物，是能特异性结合蛋白质和其它物质的DNA/RNA寡核苷酸。RNA适体由于其不稳定性和高生产成本而不受欢迎。而DNA适体由于其合成简单、稳定性好、选择性强、结合亲和力高、生产成本低等优点而受到研究者的关注。在这项研究中，我们已经成功地确定了DNA适体与EGFR的高结合亲和力和选择性。从鉴定的DNA适体中选择具有K-d 56 +/-7.3 nM的命名为TuTu 22的适体用于进一步研究。流式细胞术分析结果表明，TuTu 22适体能够特异性识别多种表达EGFR的癌细胞，但不与EGFR阴性细胞结合。由于具有上述所有优点，本文报道的针对癌症生物标志物EGFR的DNA适体将促进新型靶向癌症检测、成像和治疗的发展。(C)2014 Elsevier Inc. All rights reserved.
Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the ideal antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher's attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with K-d 56 +/- 7.3 nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy. (C) 2014 Elsevier Inc. All rights reserved.