Liquid Crystals of Nanonucleic Acids: Hierarchical Self-Assembly as a Route to Prebiotic Selection, Templating, and Autocatalysis

非技术：该奖项由科罗拉多大学博尔德分校材料研究部生物材料项目颁发，旨在开发一种化学过程，在提案中被称为“液晶自催化”。本项目探讨了益生元时代核酸出现的机制。这一建议有望通过提供基本的分子设计和原料，发展对“液晶世界”如何先于核酸世界的理解。在液晶相中，形成双相的纳米核酸端到端接触到一种结构，这种结构催化促进了它们的化学连接，这形成了自催化反馈回路的基础。这些研究的结果有可能为基于核酸的纳米技术的原位合成提供新的工具，并有可能为纳米控制的核酸和核酸的组装/拆卸提供一个全新的平台，用于不同的应用，如药物/基因传递，生物衍生马达等。拟议的教育广泛影响活动将有助于激励高中生学习STEM，并将提供宝贵的本科生研究机会。技术方面：提出的研究计划将集中于探索这个古老的液晶世界的特点，特别是它为核酸世界提供分子原料的能力。该研究将通过在更原始和多样化的初始条件下探索液晶自催化，使LC世界的输入化学原料多样化，从超短双工NAs到单碱基，再到采用益生元合成或化学降解方案制成的同源物混合物，目的是了解液晶自催化在化学噪声存在下的稳健性。该奖项将发展液晶自催化的能力，以缩小分子多样性，产生均匀的聚合物群体，如核酸。该项目还将探索LC World在生产具有化学和催化活性二级结构的核酸方面的潜力，方法是向液晶自催化系统中注入序列和长度随机的纳米核酸混合物。这种方法将有助于制定使链条能够采用二级结构的战略。该项目将从热循环和结扎的随机变化条件下开始研究核酸种群的进化，寻找特定的序列亚群或折叠基序。最后，将探索催化连接和自组装DNA化学稳定的新策略。这条路径具有明确的技术创新潜力，为巨大扩展的NA基纳米技术领域的原位合成提供了新的工具，并有可能导致纳米控制NA化学的全新平台。

Non-technical: This award by the Biomaterials program in the Division of Materials Research to the University of Colorado Boulder is to develop a chemical process, which is referred to in the proposal as "liquid crystal autocatalysis." This project explores as the mechanism for the appearance of nucleic acids in the prebiotic era. This proposal is expected to develop the understanding on how a "Liquid Crystal (LC) World" preceded the nucleic acid world by providing its basic molecular design and feedstock. Within the liquid crystal phase, duplex-forming nano-nucleic acids are held in end-to-end contact to a structure that catalytically promotes their chemical ligation, and this forms the basis for an autocatalytic feedback loop. The outcomes from these studies could have potential in offering new tools for in situ synthesis of nucleic acid-based nanotechnology, and potentially leading to a whole new platform for nano-controlled nucleic acid, and assembly/disassembly of nucleic acids for different applications such as drug/gene delivery, bioderived motors, etc. The proposed educational broader impact activities will help to inspire high school students in STEM, and would provide valuable undergraduate research opportunities. Technical: The proposed research program will be focusing on exploring the features of this ancient Liquid Crystal (LC) World and especially its capacity for providing the molecular feedstock for the nucleic acids (NAs) world. The research will diversify the input chemical stock for starting the LC World by exploring liquid crystal autocatalysis under successively more primitive and diverse initial conditions, beginning with ultra-short duplexing NAs down to single bases, and evolving to mixtures of homologs made with proposed prebiotic synthetic or chemical degradation schemes, with the goal of understanding the robustness of liquid crystal autocatalysis in the presence of chemical noise. This award will develop the ability of liquid crystal autocatalysis to narrow molecular diversity to generate homogeneous polymer populations such as the nucleic acids. This project will also explore the potential of the LC World for producing nucleic acids with chemically and catalytically active secondary structures, by feeding liquid crystal autocatalytic systems with mixtures of nanonucleic acids that incorporate randomness in sequence and lengths. This approach will enable development of strategies for making chains capable of adopting a secondary structure. This project will investigate the evolution of nucleic acid populations starting under varying conditions of randomness in thermal cycling and ligation, searching for specific subpopulations of sequences or folding motifs. Finally, new strategies will be explored for catalytic ligation and chemical stabilization of self-assembled DNA. This path has definite potential for technological novelty, offering new tools for in situ synthesis in the hugely expanding field of NA-based nanotechnology, and potentially leading to a whole new platform for nano-controlled NA chemistry.