Materials Department, University of California at Santa Barbara, Santa Barbara, CA, 93106, USA.
Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
Angew Chem Int Ed Engl. 2016 Dec 5;55(49):15258-15262. doi: 10.1002/anie.201607540. Epub 2016 Nov 3.
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.
我们首次报道了在体外选择 DNA 纳米结构的方法，这些结构在受到 pH 值变化的触发时会改变其构象。以前，大多数 pH 活性纳米结构是使用已知的 pH 活性基序设计的，例如 i-motif 或三螺旋结构。相比之下，我们从随机文库中进行了从头选择，并生成了可以响应 pH 值变化来隔离和释放米泊美生的纳米结构，米泊美生是一种临床批准的反义 DNA 药物。我们展示了非凡的 pH 选择性，在 pH 5.2 时释放的米泊美生比在 pH 7.5 时多 714 倍。有趣的是，我们的纳米结构中没有一个与已知的 pH 敏感基序有显著的序列相似性，这表明它们可能通过新的结构切换机制发挥作用。我们相信我们的选择方案是通用的，可以用于生成用于许多应用的 DNA 纳米结构，包括药物输送、传感器和 pH 活性表面。
