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

非技术性：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授予，旨在开发一种化学过程，该过程在提案中被称为“液晶自催化”。“这个项目探索了在前生物时代出现核酸的机制。这一提议有望通过提供其基本分子设计和原料来发展对“液晶（LC）世界”如何先于核酸世界的理解。在液晶相内，形成纳米核酸的纳米核酸与催化促进其化学连接的结构端对端接触，这形成了自催化反馈回路的基础。这些研究的结果可能有潜力为基于核酸的纳米技术的原位合成提供新的工具，并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/基因递送，生物衍生马达等。并将提供宝贵的本科生研究机会。 技术支持：拟议的研究计划将侧重于探索这个古老的液晶（LC）世界的特征，特别是其为核酸（NAs）世界提供分子原料的能力。 该研究将通过在连续更原始和多样化的初始条件下探索液晶自催化来使输入化学品库存多样化，开始从超短链NA到单碱基，并发展到用拟议的益生元合成或化学降解方案制成的同系物的混合物，目的是了解液晶自催化在化学噪声存在下的鲁棒性。 该奖项将开发液晶自催化的能力，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生产具有化学和催化活性二级结构的核酸的潜力，方法是向液晶自催化系统中加入纳米核酸的混合物，这些纳米核酸在序列和长度上具有随机性。这种方法将使发展战略，使链能够采用二级结构。该项目将研究在热循环和连接中不同随机条件下开始的核酸群体的进化，寻找序列或折叠基序的特定亚群。 最后，将探索新的策略，催化连接和化学稳定的自组装DNA。这条道路具有明确的技术新奇潜力，为基于NA的纳米技术领域的巨大扩展提供了原位合成的新工具，并可能为纳米控制的NA化学提供一个全新的平台。

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.