Genetic Alphabet Expansion Provides Versatile Specificities and Activities of Unnatural-Base DNA Aptamers Targeting Cancer Cells
Genetic Alphabet Expansion Provides Versatile Specificities and Activities of Unnatural-Base DNA Aptamers Targeting Cancer Cells
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DOI：
10.1016/j.omtn.2018.11.011
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发表时间：
2019-03-01
影响因子：
8.8
通讯作者：
Hirao, Ichiro
中科院分区：
文献类型：
--
作者：
Futami, Kazunobu;Kimoto, Michiko;Hirao, Ichiro
使用人工额外碱基对（非天然碱基对）的遗传字母表扩展技术的潜力一直在迅速扩大和增加。我们提出的疏水性非天然碱基7-（2-噻吩基）咪唑并[4，5-B]吡啶（Ds），作为DNA文库中的第五个字母，提供了一系列高亲和力的DNA适体，具有多种特异性和活性的结合癌细胞。这些含有Ds的DNA适体是通过一种称为cell-ExSELEX的方法产生的，靶向三种乳腺癌细胞系：MCF 7，MDA-MB-231和T-47 D。靶向MCF 7细胞的适体14 A-MCF 7特异性结合MCF 7细胞，但不结合其他癌细胞系。针对MDA-MB-231细胞的适体07-MB 231与一系列转移性骨和肺癌细胞系结合。适体05-MB 231靶向MDA-MB-231细胞，但它也结合我们检查的所有癌症和白血病细胞系。这些适体都不与正常细胞系如MCF 10A和HUVEC结合。此外，适体14 A-MCF 7和05-MB 231在癌细胞内内化，并且适体05-MB 231具有针对我们检查的大多数癌细胞系的抗增殖特性。这些适体和生成方法广泛适用于癌细胞成像、生物标志物发现、癌细胞分析、抗癌疗法和药物递送系统。
The potential of genetic alphabet expansion technologies using artificial extra base pairs (unnatural base pairs) has been rapidly expanding and increasing. We present that the hydrophobic unnatural base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds), which acts as a fifth letter in a DNA library, provides a series of high-affinity DNA aptamers with versatile binding specificities and activities to cancer cells. These Ds-containing DNA aptamers were generated by a method called cell-ExSELEX to target three breast cancer cell lines: MCF7, MDA-MB-231, and T-47D. Aptamer 14A-MCF7, which targets MCF7 cells, specifically binds to MCF7 cells, but not other cancer cell lines. Aptamer 07-MB231, which targets MDA-MB-231 cells, binds to a series of metastatic bone and lung cancer cell lines. Aptamer 05-MB231 targets MDA-MB-231 cells, but it also binds to all of the cancer and leukemia cell lines that we examined. None of these aptamers bind to normal cell lines, such asMCF10A and HUVEC. In addition, aptamers 14A-MCF7 and 05-MB231 are internalized within the cancer cells, and aptamer 05-MB231 possesses anti-proliferative properties against most cancer cell lines that we examined. These aptamers and the generation method are broadly applicable to cancer cell imaging, biomarker discovery, cancer cell profiling, anti-cancer therapies, and drug delivery systems.