Molecular targeted drug discovery for cancer cell radiosensitization using RNA aptamars

众所周知，阻断与DNA修复机制相关的蛋白激酶如DNA-PKcs、ATM或ATR可增强对电离辐射（IR）的敏感性。从这个角度来看，我们预计，肿瘤细胞对放射治疗的敏感性提高，通过利用这一机制。与DNA修复机制相关的蛋白激酶通过磷酸化被激活。因此，我们尝试利用RNA工程技术，研制新型放射增敏药物作为肿瘤的分子靶向药物。本实验利用SELEX技术制备了针对DNA-PKcs磷酸化位点的RNA适体。在本研究中，我们制备了针对DNA-PKcs磷酸化位点的RNA适体。进一步利用新一代测序技术分析了它们的特异性模板序列，并对其中可能特异识别DNA-PKcs的序列进行了重点分析。用RNA分子转染U2 OS细胞，我们测试是否可以增加辐射敏感性。总之，我们发现了一些RNA分子，提高辐射敏感性的U2 OS细胞。

It is well known that blocking protein kinases related to DNA repair machinery such as DNA-PKcs, ATM, or ATR enhance sensitivity to ionizing radiation (IR). From this point of view, we expect that tumor cell sensitivity against radiotherapy is enhanced by exploiting this mechanism. Protein kinases related to DNA repair machinery are activated by being phosphorylated. Therefore we attempted making the RNA engineering technology, and will develop new radiation sensitization medicine as a molecular target drug for cancer. In this experiment, we are making RNA aptamers against phosphorylated site of DNA-PKcs by SELEX. In this research, we produced RNA aptamers specific to DNA-PKcs phosphorylation site. Furtheremore their specific template sequences were analyzed by next-generation sequencing technology, and some that may recognize DNA-PKcs specifically were focused. U2OS cells are transfected with the RNA molecules, we tested whether can increase sensitivity of radiation. In conclusion, we found some RNA molecules that enhance sensitivity of radiation for U2OS cells.