In Vitro Selection of pH-Activated DNA Nanostructures.
In Vitro Selection of pH-Activated DNA Nanostructures.
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DOI：
10.1002/anie.201607540
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发表时间：
2016-12-05
期刊：
影响因子：
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通讯作者：
Soh HT
中科院分区：
文献类型：
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作者：
Fong FY;Oh SS;Hawker CJ;Soh HT
我们报告的第一个在体外选择的DNA纳米结构，切换其构象时，触发pH值的变化。以前，大多数pH活性纳米结构设计使用已知的pH活性基序，如i-基序或三链体结构。相比之下，我们从随机文库开始进行从头选择，并产生可以螯合和释放Mipomersen（一种临床批准的反义DNA药物）的纳米结构，以响应pH值的变化。我们展示了非凡的pH选择性，在pH 5.2下释放的米泊美生是pH 7.5下的714倍。有趣的是，我们的纳米结构都没有显示出与已知pH敏感基序的显着序列相似性，这表明它们可能通过新的结构转换机制进行操作。我们相信我们的选择方案是通用的，可以用于产生DNA纳米结构的许多应用，包括药物输送，传感器和pH活性表面。一种新的定向进化方法来产生DNA纳米结构，该纳米结构可以响应pH变化捕获和释放反义DNA有效载荷。实现了高度pH选择性释放，其中与pH 7.5相比，在pH 5.2下释放高达714倍的有效负载。这些分子在药物输送、传感器和pH敏感纳米材料方面具有潜在的应用。
We report the first in vitro selection of DNA nanostructures that switch their conformation when triggered by change in pH. Previously, most pH-active nanostructures were designed using known pH-active motifs, such as the i-motif or the triplex structure. In contrast, we performed de novo selections starting from a random library and generated nanostructures that can sequester and release Mipomersen, a clinically approved antisense DNA drug, in response to pH change. We demonstrate extraordinary pH-selectivity, releasing up to 714-fold more Mipomersen at pH 5.2 compared to pH 7.5. Interestingly, none of our nanostructures showed significant sequence similarity to known pH-sensitive motifs, suggesting that they may operate via novel structure-switching mechanisms. We believe our selection scheme is general and could be adopted for generating DNA nanostructures for many applications including drug delivery, sensors and pH-active surfaces. A new directed evolution method to generate DNA nanostructures which can catch and release an antisense DNA payload in response to pH change. Highly pH-selective release was achieved where up to 714-fold more payload was released at pH 5.2 compared to pH 7.5. These molecules have potential applications in drug delivery, sensors, and pH-sensitive nanomaterials.