Intelligent demethylase-driven DNAzyme sensor for highly reliable metal-ion imaging in living cells.

Intelligent demethylase-driven DNAzyme sensor for highly reliable metal-ion imaging in living cells.
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智能去甲基化酶驱动的 DNAzyme 传感器,可在活细胞中实现高度可靠的金属离子成像

DOI:
10.1039/d1sc05370a
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发表时间:
2021-12-01
期刊:
影响因子:
8.4
通讯作者:
Wang F
Wang F
中科院分区:
化学1区
文献类型:
--
作者:
Hong C;Wang Q;Chen Y;Gao Y;Shang J;Weng X;Liu X;Wang F

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金属离子的精确细胞内成像需要对金属离子传感器进行精确的位点特异性激活,而普遍的表观遗传调控策略由于其正交控制特征和内源性细胞/组织特异性表达模式可以作为理想的替代方案。在此,提出了一种简单而通用的去甲基化策略,用于现场修复激活金属离子靶向脱氧核糖核酸酶,并实现活细胞中金属离子的精确位点特异性成像。这种内源性表观遗传去甲基化调节DNAzyme系统是通过用m6A甲基化基团修饰DNAzyme来制备的,该甲基化基团使DNAzyme探针失能,从而消除了可能的异位信号泄漏,而细胞特异性去甲基化酶介导的甲基化修饰去除可以有效恢复传感金属离子的初始催化DNAzyme,从而在活细胞中实现高对比度生物成像。这种表观遗传修复激活 DNAzyme 策略可能有助于疾病特异性生物标志物的稳健可视化,以深入探索其生物学功能。
The accurate intracellular imaging of metal ions requires an exquisite site-specific activation of metal-ion sensors, for which the pervasive epigenetic regulation strategy can serve as an ideal alternative thanks to its orthogonal control feature and endogenous cell/tissue-specific expression pattern. Herein, a simple yet versatile demethylation strategy was proposed for on-site repairing-to-activating the metal-ion-targeting DNAzyme and for achieving the accurate site-specific imaging of metal ions in live cells. This endogenous epigenetic demethylation-regulating DNAzyme system was prepared by modifying the DNAzyme with an m6A methylation group that incapacitates the DNAzyme probe, thus eliminating possible off-site signal leakage, while the cell-specific demethylase-mediated removal of methylation modification could efficiently restore the initial catalytic DNAzyme for sensing metal ions, thus allowing a high-contrast bioimaging in live cells. This epigenetic repair-to-activate DNAzyme strategy may facilitate the robust visualization of disease-specific biomarkers for in-depth exploration of their biological functions.
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