A modular clamp-like mechanism to regulate the activity of nucleic-acid target-responsive nanoswitches with external activators
A modular clamp-like mechanism to regulate the activity of nucleic-acid target-responsive nanoswitches with external activators
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DOI：
10.1039/c6nr06026a
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发表时间：
2016-11-14
期刊：
影响因子：
6.7
通讯作者：
Ricci, Francesco
中科院分区：
文献类型：
--
作者：
Del Grosso, Erica;Idili, Andrea;Ricci, Francesco
在这里，我们展示了一个通用的和模块化的方法来调节目标响应的DNA为基础的纳米开关的活动。我们通过将两个基于DNA的响应元件偶联在一起来做到这一点：能够结合特定DNA序列的三链体形成钳状探针和选择用于结合小分子的分裂适体。在存在上述响应元件之一的特异性靶标的情况下，纳米开关部分折叠并且其结合第二靶标的能力恢复。通过这种方法，我们可以使用外部配体精细地调节DNA识别元件和适体的亲和力。我们的策略的模块化性质使得它很容易推广到不同的基于DNA的识别元件。为了证明这一点，我们成功地设计了五种不同的DNA纳米开关，其响应性可以由不同的分子效应器和靶标调节。设计这种机制的便利性表明，它可能证明是一种有用的工具，通过这种工具，可以用外部输入控制传感器、遗传网络和采用基于核酸的受体的其他生物技术装置。
Here we demonstrate a general and modular approach to regulate the activity of target-responsive DNA-based nanoswitches. We do so by coupling together two DNA-based responsive elements: a triplex-forming clamp-like probe able to bind a specific DNA sequence and a split aptamer selected to bind a small molecule. In the presence of the specific target of one of the above responsive elements, the nanoswitch partially folds and its ability to bind the second target is restored. With this approach we can finely modulate the affinity of both DNA-recognition elements and aptamers using an external ligand. The modular nature of our strategy makes it easily generalizable to different DNA based recognition elements. As a demonstration of this we successfully designed five different DNA nanoswitches whose responsiveness can be regulated by different molecular effectors and targets. The convenience with which this mechanism is designed suggests that it may prove a useful tool by which sensors, genetic networks and other biotechnology devices employing nucleic-acid based receptors can be controlled with an external input.