In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.
In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.
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DOI：
10.1021/nn404079v
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发表时间：
2013-11-26
期刊：
影响因子：
17.1
通讯作者：
Soh, H. Tom
中科院分区：
文献类型：
--
作者：
Oh, Seung Soo;Plakos, Kory;Xiao, Yi;Eisenstein, Michael;Soh, H. Tom
许多生物系统采用变构调节机制，其提供了将特异性结合事件直接连接到宽范围的分子功能的有力手段。人们对产生合成的变构调节剂有相当大的兴趣，所述变构调节剂可以在诊断、成像和靶向治疗中的应用中执行有用的分子功能，但是通过合理设计或定向进化产生这样的分子已经被证明是非常具有挑战性的。为了满足这一需求，我们提出了一种体外选择策略，用于生成构象转换DNA纳米结构，该结构响应于特定触发分子的结合而选择性地释放小分子有效载荷。作为一个例子，我们已经产生了一个DNA纳米结构，与一个单独的“货物链”含有脱碱基位点杂交。该脱碱基位点稳定地螯合处于非活性状态的荧光货物分子，直到DNA纳米结构遇到ATP触发分子。这种ATP触发剂导致纳米结构释放货物链，从而释放荧光有效载荷并产生可检测的荧光读数。我们的DNA纳米结构具有高度敏感性，EC50为30 μM，并且具有高度特异性，释放其有效载荷以响应ATP，但不响应其他化学相似的核苷酸三磷酸。我们相信，这种选择方法可以推广到生成合成纳米结构，能够选择性和控制释放其他小分子货物，以响应各种触发器，用于研究和临床应用。
Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate ‘cargo strand’ containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.
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影响因子：
7.4
作者：
Oh, Seung Soo;Ahmad, Kareem M.;Cho, Minseon;Kim, Seon;Xiao, Yi;Soh, H. Tom
通讯作者：
Soh, H. Tom
影响因子：
3.7
作者：
Ahmad KM;Oh SS;Kim S;McClellen FM;Xiao Y;Soh HT
通讯作者：
Soh HT
影响因子：
62.1
作者：
Liu, Juewen;Cao, Zehui;Lu, Yi
通讯作者：
Lu, Yi
影响因子：
7
作者：
Heid, CA;Stevens, J;Williams, PM
通讯作者：
Williams, PM
影响因子：
15
作者：
Nutiu, R;Li, YF
通讯作者：
Li, YF