Three-Dimensional DNA Nanostructures for Biological and Materials Applications

我们的研究小组专注于使用生物分子DNA在纳米尺度上实现可编程组织。 在过去的五年里，我们已经展示了简单有效的方法来构建一系列3D-DNA笼和纳米管，并完全控制尺寸和形状。这些结构可以封装货物并响应于特定的生物分子释放它，并且它们可以在没有转染试剂的帮助下穿过许多哺乳动物细胞的质膜。 该提案旨在对这些高度组织化的DNA纳米结构如何相互作用以及与其他生物结构相互作用进行基本了解。 我们描述了蛋白质启发的功能性DNA结构的设计，其结构域与战略定位的侧链相关联。我们使用超分子相互作用（疏水，金属配位，静电等）一起合作 除了在不使用数百种不同DNA序列的情况下将复杂性引入DNA纳米技术之外，这些研究还将增加我们对蛋白质折叠问题的理解。 这项工作将开发DNA笼，用于封装小分子货物，并在存在生物触发因素（例如mRNA、蛋白质或疾病环境中的分子）的情况下释放它，以实现潜在的靶向药物递送。 我们展示了一种将3D序列信息从DNA笼转移到交联纳米颗粒中的方法，所述交联纳米颗粒是单分散的并且具有确定数量的DNA臂和方向。 这将导致新一代精确图案化的功能材料应用于纳米电子学，纳米光学和光捕获。

Our research group focuses on using the biological molecule DNA to achieve programmable organization on the nanometer scale. In the past five years, we have shown simple and efficient methods to construct a range of 3D-DNA cages and nanotubes, with full control of size and shape. These structures can encapsulate cargo and release it in response to specific biological molecules, and they can travel across the plasma membrane of a number of mammalian cells, without the aid of transfection reagents. This proposal seeks to develop a fundamental understanding of how these highly organized DNA nanostructures interact with each other, and with other biological structures. We describe the protein-inspired design of functional DNA structures, whose domains associate together with strategically positioned side-chains. We use supramolecular interactions (hydrophobic, metal coordination, electrostatic, etc.) working together in concert. In addition to introducing complexity into DNA nanotechnology without using hundreds of different DNA sequences, these studies will increase our understanding of the protein folding problem. This work will develop DNA cages that encapsulate small molecule cargo and release it in the presence of a biological trigger, such as mRNA, proteins or molecules in a disease environment, for potential targeted drug delivery. We show a method to transfer the 3D-sequence information from a DNA cage, into crosslinked nanoparticles that are monodisperse and that possess a defined number of DNA arms and orientations. This will lead to a new generation of precisely patterned, functional materials for applications in nanoelectronics, nanooptics and light-harvesting.