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首页> 外文期刊>Biomaterials Science >Rapid identification of specific DNA aptamers precisely targeting CD33 positive leukemia cells through a paired cell-based approach
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Rapid identification of specific DNA aptamers precisely targeting CD33 positive leukemia cells through a paired cell-based approach

机译：通过配对的基于细胞的方法快速鉴定特异性DNA适体的特定DNA适体细胞的靶向CD33阳性白血病细胞

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摘要

Aptamers are short single-stranded DNA or RNA molecules, which have recently been developed for potential broad applications such as clinical therapeutics, diagnosis and tumor-targeted drug delivery. However, the selection of specific aptamers is often unsatisfactory using the classical protein or cell-based SELEX. Herein, we modified the paired cell line approach to identify aptamers targeting leukemia cells expressing the CD33 antigen. Our strategy artfully used the same cells for negative (HEK293T cells) and positive (CD33 transfected-HEK293T cells) aptamer selections, and the negative selections were performed adequately before the positive selection to remove unspecific sequences. The advantages of this strategy are that it is fast and accurate, where only a few rounds of selection together with PCR amplifications are sufficient to obtain high binding affinity antigen-targeted aptamers. By using our modified approach, we successfully obtained the CD33-targeting aptamer S30, which could highly recognize the C2 domain of the CD33 antigen in vitro and in vivo. Moreover, the optimized aptamer S30-T1 (i.e., core region of S30) was conjugated with doxorubicin (Dox) to synthesize S30-T1-Dox conjugates, which could specifically inhibit CD33 positive acute myeloid leukemia HL-60 cell proliferation by arresting the cell cycle at the G2 phase. Thus, our modified approach can rapidly screen reliable, stable and high binding affinity aptamers for precise cancer treatment.
机译：适体是短的单链DNA或RNA分子，最近已开发用于潜在的广泛应用，例如临床治疗，诊断和肿瘤靶向药物递送。然而，使用典型蛋白质或基于细胞的SELEX的特异性适体的选择通常不令人满意。在此，我们修饰了配对的细胞系方法以鉴定靶向表达CD33抗原的白血病细胞的适体。我们的策略符合阴性（HEK293T细胞）和阳性（CD33转染 - HEK293T细胞）适体选择的相同细胞，并且在阳性选择之前充分执行负选择以去除非特异性序列。该策略的优点是它是快速准确的，其中只有几轮选择与PCR扩增的选择足以获得高结合亲和抗原靶向适体。通过使用我们的修饰方法，我们成功地获得了CD33靶向适体S30，其可以高度识别在体外和体内CD33抗原的C2结构域。此外，优化的适体S30-T1（即S30的核心区域）与多柔比蛋白（DOX）缀合，以合成S30-T1-DOX缀合物，其通过捕获细胞来特异性地抑制CD33阳性急性骨髓白血病HL-60细胞增殖在G2阶段循环。因此，我们改性方法可以迅速筛选可靠，稳定，高结合亲和力适体，用于精确癌症治疗。

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  • 来源
    《Biomaterials Science》 |2019年第3期|共13页
  • 作者

    Yang Chang; Wang Yun; Ge Ming Hua; Fu Yu Jie; Hao Rui; Islam Khairul; Huang Ping; Chen Fu; Sun Jie; Hong De Fei; Naranmandura Hua;

  • 作者单位

    Zhejiang Univ Sch Med Dept Pharmacol Hangzhou 310058 Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Dept Pharmacol Hangzhou 310058 Zhejiang Peoples R China;

    Zhejiang Canc Hosp Hangzhou 310022 Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Dept Pharmacol Hangzhou 310058 Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Dept Pharmacol Hangzhou 310058 Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Dept Pharmacol Hangzhou 310058 Zhejiang Peoples R China;

    Zhejiang Canc Hosp Hangzhou 310022 Zhejiang Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Zhejiang Peoples R China;

    Zhejiang Univ Affiliated Hosp 1 Dept Hematol Hangzhou 310003 Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Affiliated Sir Run Run Shaw Hosp Hangzhou 310016 Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Dept Pharmacol Hangzhou 310058 Zhejiang Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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