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Evolution of Nucleic Acid Aptamers Capable of Specifically Targeting Glioma Stem Cells via Cell-SELEX

机译:能够通过细胞分解物特异性靶向胶质瘤干细胞的核酸适体的演变

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摘要

Glioma stem cells (GSCs), a particular group of cells from gliomas, are capable of infinite proliferation and differentiation. Recent studies have shown that GSCs may be the root of tumor recurrence, metastasis, and resistance. Early detection and targeted therapy of GSCs may significantly improve the survival rate of glioma patients. Therefore, molecular ligands capable of selectively recognizing GCSs are of great importance. The objective of this study is to generate DNA aptamers for selective identification of the molecular signature of GSCs using cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX). GSCs were used as the positive selection target, while U87 cells were used in negative cycles for removal of DNA molecules binding to common glioma cell lines. Finally, we successfully identified one aptamer named W5-7 with a K-d value of 4.9 +/- 1.4 nM. The sequence of the aptamer was further optimized, and its binding target was identified as a membrane protein. The aptamer W5-7 was stable in cerebral spinal fluid over 36 h and could also effectively detect glioma stem cells in cerebral spinal fluid samples. With its superb targeting properties and functional versatility, WS-7 holds great potential for use as a molecular probe for detecting and isolating GSCs.
机译:胶质瘤干细胞(GSCs),来自胶质瘤的特定细胞组能够无限增殖和分化。最近的研究表明,GSC可能是肿瘤复发,转移和抗性的根本。 GSCs的早期检测和靶向治疗可能会显着提高胶质瘤患者的存活率。因此,能够选择性地识别GCSS的分子配体具有重要意义。本研究的目的是生成DNA适体,用于使用基于细胞的系统演化通过指数富集(细胞 - SELEX)选择性地鉴定GSCs的分子签名。 GSCS被用作阳性选择靶标,而U87细胞用于负循环中,用于去除与常见的胶质瘤细胞系结合的DNA分子。最后,我们成功地标识了一个名为W5-7的一个适体,K-D值为4.9 +/- 1.4 nm。进一步优化适体的序列,其结合靶标被鉴定为膜蛋白。适体W5-7在脑脊柱液中稳定在36小时,也可以有效地检测脑脊髓样品中的胶质瘤干细胞。通过其精湛的靶向性和功能性多功能性,WS-7具有很大的用作用于检测和隔离GSC的分子探针。

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  • 来源
    《Analytical chemistry》 |2019年第13期|共8页
  • 作者单位

    Fujian Med Univ Clin Med Coll 1 Affiliated Hosp 1 Dept Neurosurg Dept Emergency Surg Fuzhou 350004 Fujian Peoples R China;

    Fujian Med Univ Clin Med Coll 1 Affiliated Hosp 1 Dept Neurosurg Dept Emergency Surg Fuzhou 350004 Fujian Peoples R China;

    Xiamen Univ Coll Chem &

    Chem Engn Dept Chem Biol MOE Key Lab Spectrochem Anal &

    Instrumentat State Key Lab Phys Chem Solid Surfaces Key Lab Ch Xiamen 361005 Fujian Peoples R China;

    Xiamen Univ Coll Chem &

    Chem Engn Dept Chem Biol MOE Key Lab Spectrochem Anal &

    Instrumentat State Key Lab Phys Chem Solid Surfaces Key Lab Ch Xiamen 361005 Fujian Peoples R China;

    Fujian Med Univ Clin Med Coll 1 Affiliated Hosp 1 Dept Neurosurg Dept Emergency Surg Fuzhou 350004 Fujian Peoples R China;

    Fujian Med Univ Clin Med Coll 1 Affiliated Hosp 1 Dept Neurosurg Dept Emergency Surg Fuzhou 350004 Fujian Peoples R China;

    Fujian Med Univ Clin Med Coll 1 Affiliated Hosp 1 Dept Neurosurg Dept Emergency Surg Fuzhou 350004 Fujian Peoples R China;

    Fujian Med Univ Clin Med Coll 1 Affiliated Hosp 1 Dept Neurosurg Dept Emergency Surg Fuzhou 350004 Fujian Peoples R China;

    Southern Univ Sci &

    Technol Dept Chem Guangdong Prov Key Lab Cell Microenvironm &

    Dis R Shenzhen 518055 Peoples R China;

    Xiamen Univ Coll Chem &

    Chem Engn Dept Chem Biol MOE Key Lab Spectrochem Anal &

    Instrumentat State Key Lab Phys Chem Solid Surfaces Key Lab Ch Xiamen 361005 Fujian Peoples R China;

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  • 正文语种 eng
  • 中图分类 分析化学;
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