Membrane Scaffolds Enhance the Responsiveness and Stability of DNA-Based Sensing Circuits

Membrane Scaffolds Enhance the Responsiveness and Stability of DNA-Based Sensing Circuits
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DOI:
10.1021/acs.bioconjchem.9b00080
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发表时间:
2019-07-01
影响因子:
4.7
通讯作者:
Di Michele, Lorenzo
Di Michele, Lorenzo
中科院分区:
化学2区
文献类型:
--
作者:
Kaufhold, Will T.;Brady, Ryan A.;Di Michele, Lorenzo

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靶诱导的DNA链置换是开发用于临床诊断和合成生物学的分析物响应DNA电路的极好候选者。虽然大多数可用的技术依赖于DNA电路自由扩散的散装,在这里,我们探索使用脂质体作为基于DNA的传感纳米器件的支架。我们的概念验证传感电路通过释放DNA链来响应模型目标分析物的存在,这反过来又激活荧光报告。通过实验和粗粒度蒙特卡罗模拟相结合,我们证明了膜支架的存在加速了寡核苷酸释放的过程,抑制了不需要的泄漏反应,使传感器的响应性和鲁棒性更强。
Target-induced DNA strand displacement is an excellent candidate for developing analyte-responsive DNA circuitry to be used in clinical diagnostics and synthetic biology. While most available technologies rely on DNA circuitry free to diffuse in bulk, here we explore the use of liposomes as scaffolds for DNA-based sensing nanodevices. Our proof-of-concept sensing circuit responds to the presence of a model target analyte by releasing a DNA strand, which in turn activates a fluorescent reporter. Through a combination of experiments and coarse-grained Monte Carlo simulations, we demonstrate that the presence of the membrane scaffold accelerates the process of oligonucleotide release and suppresses undesired leakage reactions, making the sensor both more responsive and robust.