Opazo Felipe, Eiden Laura, Hansen Line, Rohrbach Falk, Wengel Jesper, Kjems Jørgen, Mayer Günter
Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Göttingen, Germany.
Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
Mol Ther Nucleic Acids. 2015 Sep 1;4(9):e251. doi: 10.1038/mtna.2015.25.
Aptamers are valuable tools that provide great potential to develop cost-effective diagnostics and therapies in the biomedical field. Here, we report a novel DNA aptamer that folds into an unconventional G-quadruplex structure able to recognize and enter specifically into human Burkitt's lymphoma cells. We further optimized this aptamer to a highly versatile and stable minimized version. The minimized aptamer can be easily equipped with different functionalities like quantum dots, organic dyes, or even a second different aptamer domain yielding a bi-paratopic aptamer. Although the target molecule of the aptamer remains unknown, our microscopy and pharmacological studies revealed that the aptamer hijacks the clathrin-mediated endocytosis pathway for its cellular internalization. We conclude that this novel class of aptamers can be used as a modular tool to specifically deliver different cargoes into malignant cells. This work provides a thorough characterization of the aptamer and we expect that our strategy will pave the path for future therapeutic applications.
适体是一种有价值的工具，在生物医学领域开发具有成本效益的诊断和治疗方法方面具有巨大潜力。在此，我们报告了一种新型DNA适体，它折叠成一种非常规的G-四链体结构，能够识别并特异性进入人伯基特淋巴瘤细胞。我们进一步将这种适体优化为一个高度通用且稳定的最小化版本。该最小化适体可以轻松配备不同的功能，如量子点、有机染料，甚至是第二个不同的适体结构域，从而产生双特异性适体。尽管该适体的靶分子仍然未知，但我们的显微镜和药理学研究表明，该适体通过网格蛋白介导的内吞途径进入细胞。我们得出结论，这类新型适体可作为一种模块化工具，将不同的货物特异性递送至恶性细胞中。这项工作对该适体进行了全面表征，我们期望我们的策略将为未来的治疗应用铺平道路。
