Supramolecular DNA Structures: From Design to Function

超分子 DNA 结构：从设计到功能

• 批准号: RGPIN-2018-06861
• 负责人: Sleiman, Hanadi
• 金额: $ 20.11万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748096
• 关键词: Supramolecular; DNA; Structures; Design; Function

Our research during the last 6 years has led to several discoveries in the fields of supramolecular chemistry and DNA nanotechnology. These include:(a) DNA cages that encapsulate therapeutics and release them selectively, only when they encounter a molecule that is present in cancer cells, and that have favorable in vitro and in vivo properties of these structures. (b) the observation that DNA nanostructures can be used as a temporary “printing press” rather than a permanent scaffold, and can transfer their structural information to gold particles and polymers. This introduces the notion that supramolecular information can be chemically transmitted from one material to another. (c) an alternative method to expand the DNA base-pairing code, by adding a small hydrogen-bonding molecule that reprograms DNA base-pairing into a “rosette” motif.(d) a new class of polymers which are monodisperse and sequence-controlled, synthesized by adapting the tools of automated solid-phase DNA synthesis. Combining them with DNA nanostructures leads to emergent assembly modes which could not have been obtained by either material.(e) the building of complex DNA structures by controlling the order of addition of their components which can then be re-used, thus using temporal control to achieve complexity. This proposal describes the use of DNA assembly to bring unprecedented structural definition and dynamic character to two important classes of materials: synthetic polymers and lipid bilayers. Interaction of DNA nanostructures with lipid bilayer membranes. DNA cages have tremendous potential for sensing, imaging, and drug delivery applications. The first interface that they encounter when they interact with cells are lipid bilayer membranes, and thus understanding this process is essential to transition them to biological applications. In this proposal, we examine the interaction of DNA nanostructures with lipid bilayers and develop two applications for these materials: as membrane nanopores for biomolecule detection, and as rafts' to mediate cell attachment and tune membrane curvature.Molecular “Printing” on Polymers with DNA Structures. We will build upon our recent discovery that DNA nanostructures can be used as a temporary template, or a “printing press”. There has been tremendous interest and elegant methods to increase the complexity of polymer nanostructures. However, the structural definition of DNA and its programmability are unmatched in polymer chemistry. We will describe the use of DNA structures as templates to covalently attach DNA patterns to polymeric nanoparticles in 2D- and 3D-, and to control their size and shape with DNA molding' strategies. This results in unprecedented polymer particles that assemble in a directional manner, the way that atoms come together to make molecules, thus dramatically increasing the level of control and programmability in polymer self-assembly.

在过去的6年里，我们的研究在超分子化学和DNA纳米技术领域取得了几项发现。其中包括：(A)包裹治疗药物并选择性地释放它们的DNA笼子，只有当它们遇到癌细胞中存在的分子，并且在体外和体内具有良好的这些结构的性质时，才能有选择地释放它们。(B)观察到DNA纳米结构可用作临时“印刷机”，而不是永久支架，并可将其结构信息转移到金粒子和聚合物上。这引入了超分子信息可以从一种材料化学传输到另一种材料的概念。(C)扩展DNA碱基配对密码的另一种方法，增加一个小的氢键分子，将DNA碱基配对重新编程为“玫瑰”基序。(D)一类新的单分散和顺序控制的聚合物，通过采用自动固相DNA合成的工具合成。将它们与DNA纳米结构相结合，产生了任何一种材料都无法获得的紧急组装模式。(E)通过控制其组件的添加顺序来构建复杂的DNA结构，然后这些组件可以重复使用，从而使用时间控制来实现复杂性。这项提议描述了利用DNA组装给两类重要的材料带来前所未有的结构定义和动态特性：合成聚合物和脂类双层。DNA纳米结构与脂质双层膜的相互作用。DNA笼在传感、成像和药物输送应用方面具有巨大的潜力。当它们与细胞相互作用时，它们遇到的第一个界面是脂质双层膜，因此了解这一过程对于将它们转化为生物应用是至关重要的。在这个方案中，我们研究了DNA纳米结构与脂质双层之间的相互作用，并开发了这些材料的两个应用：作为膜纳米孔用于生物分子检测，以及作为筏子用于介导细胞附着和调节膜曲率。分子打印在具有DNA结构的聚合物上。我们将建立在我们最近的发现的基础上，DNA纳米结构可以用作临时模板，或“印刷机”。人们对增加聚合物纳米结构的复杂性有极大的兴趣和巧妙的方法。然而，DNA的结构定义及其可编程性在聚合物化学中是无与伦比的。我们将描述使用DNA结构作为模板，以2D和3D形式将DNA图案共价连接到聚合纳米颗粒上，并通过DNA成型策略控制其大小和形状。这导致了前所未有的聚合物粒子以定向的方式组装，也就是原子聚集成分子的方式，从而极大地提高了聚合物自组装的控制水平和可编程性。