Zhu Longyi, Shen Yiting, Deng Shengyuan, Wan Ying, Luo Jun, Su Yan, You Mingxu, Fan Chunhai, Ren Kewei
School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology Nanjing 210094 China
School of Environmental and Biological Engineering, Nanjing University of Science and Technology Nanjing 210094 China.
Chem Sci. 2023 Jul 6;14(30):8084-8094. doi: 10.1039/d2sc07095b. eCollection 2023 Aug 2.
DNA nanodevices have been feasibly applied for various chemo-biological applications, but their functions as precise regulators of intracellular organelles are still limited. Here, we report a synthetic DNA binder that can artificially induce mitochondrial aggregation and fusion in living cells. The rationally designed DNA binder consists of a long DNA chain, which is grafted with multiple mitochondria-targeting modules. Our results indicated that the DNA binder-induced self-assembly of mitochondria can be used to successfully repair ROS-stressed neuron cells. Meanwhile, this DNA binder design is highly programmable. Customized molecular switches can be easily implanted to further achieve stimuli-triggered mitochondrial aggregation and fusion inside living cells. We believe this new type of DNA regulator system will become a powerful chemo-biological tool for subcellular manipulation and precision therapy.
DNA纳米器件已被切实应用于各种化学生物学应用中,但其作为细胞内细胞器精确调节器的功能仍然有限。在此,我们报告一种合成DNA结合剂,它可以在活细胞中人工诱导线粒体聚集和融合。这种经过合理设计的DNA结合剂由一条长DNA链组成,该链上接有多个线粒体靶向模块。我们的结果表明,DNA结合剂诱导的线粒体自组装可成功用于修复受活性氧应激的神经元细胞。同时,这种DNA结合剂设计具有高度的可编程性。定制的分子开关可以很容易地植入,以进一步实现活细胞内刺激触发的线粒体聚集和融合。我们相信这种新型的DNA调节系统将成为用于亚细胞操作和精准治疗的强大化学生物学工具。