Collaborative Research: Exploring self-organization of functional nucleic acid supramolecular assemblies with stimuli responsive properties

该项目由生物材料计划和刺激竞争性研究的既定计划（EPSCoR）联合资助。第1部分：非技术概述核糖核酸或RNA的研究对于理解生命所需的主要细胞过程以及各种疾病的起源至关重要。通过使用合理设计的rna作为构建块，可以组装具有预定义属性和结构的核酸纳米颗粒（NANPs）。易于对生物环境变化作出反应的能力使生物相容性纳米粒子成为临床应用的有吸引力的材料。此外，NANPs的生化通用性可以与无机纳米材料的光学、电子和磁性相结合。这些增强的NANPs可以被组织成具有控制复杂性和功能的超分子组件，适用于广泛的生物医学，电子和成像应用。然而，尽管最近取得了进展，但设计复杂，响应灵敏，具有调节形态的NANP超组件仍然是一个挑战。拟议的研究计划旨在开发一个通用的工具包，用于为生物技术的最终用户设计基于刺激响应的纳米粒子材料。构建功能性NANP超组装体将改善当前治疗系统的性能，允许可重构生物材料的工程，并有助于进一步理解内源性生物分子功能的相互作用。在这个项目中，本科生和研究生将接受实验和计算RNA纳米技术的多学科培训。该项目还将扩展名为ouRNAno的教育领域，向社区通报RNA纳米技术领域的最新进展，并将通过与当地学校和科学博物馆举办社区STEM活动，继续培养对研究的兴趣。RNA纳米技术得益于RNA通过规范和非规范碱基对（形成12个几何家族）进行组装的能力。这提供了一套多样的结构和相互作用的基序，允许构建核酸纳米颗粒（NANPs）。纳米粒子的多用途生物化学特性可以与无机纳米材料的光学、电子和磁性相结合。这些增强的纳米粒子进一步组织成合理设计的超分子组装体，具有可控的结构复杂性，可用于生物光学、响应装置的设计、柔性仿生机器、组织模拟和人造肌肉。尽管存在用于NANP设计的计算工具，但使用NANP作为超分子组装的模块化构建块从未被系统地研究过。因此，本研究项目旨在通过开发一种可通用的基于nanp的可编程平台来解决这一知识空白，该平台通过独立可编程的结构参数网络同时编码目标物理化学，机械和生物特性。为了实现这些目标，该团队提出了三个主要目标：(i)将NANPs的可编程参数与其超分子组件的物理化学和机械性能相关联；（ii）评估单个纳米粒子与无机纳米材料的功能化对其超分子组件的物理化学和机械性能的影响；（iii）研究刺激依赖的动力学途径对功能性超分子组装性质的影响。该项目将大大推进NANP超组件作为新型刺激响应材料的工程框架，并使其在生物医学、电子和成像应用领域得到广泛应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project is jointly funded by the Biomaterials program and the Established Program to Stimulate Competitive Research (EPSCoR)PART 1: NON-TECHNICAL SUMMARYThe study of ribonucleic acid or RNA is essential for understanding major cellular processes needed for life as well as the origin of various diseases. By using rationally designed RNAs as building blocks, it becomes possible to assemble Nucleic Acid NanoParticles, or NANPs, with pre-defined properties and architectures. The ability to readily respond to changes in biological environments makes biocompatible NANPs an attractive material for clinical use. Also, the biochemical versatility of NANPs can be combined with the optical, electronic, and magnetic properties of inorganic nanomaterials. These augmented NANPs can then be organized into supramolecular assemblies with controlled complexity and functions suitable for a broad range of biomedical, electronic, and imaging applications. However, despite the recent progress, it is still a challenge to engineer sophisticated, responsive, NANP supra-assemblies with regulated morphology. The proposed research program aims to develop a generalizable toolkit for the construction of stimuli-responsive NANP-based materials designed for end users in biotechnology. Building functional NANP supra-assemblies will improve the performance of current therapeutic systems, allow for the engineering of reconfigurable biomaterials, and become instrumental in furthering our understanding of the interactions governing the function of endogenous biomolecules. During this program, the undergraduate and graduate students will receive multidisciplinary training in experimental and computational RNA nanotechnology. This project will also expand the educational domain called ouRNAno that reaches out to and informs the community about recent advances in the field of RNA nanotechnology and will continue cultivating excitement for research through hosting community STEM events with local schools and science museum. PART 2: TECHNICAL SUMMARYRNA nanotechnology benefits from RNA’s ability to assemble through both canonical and non-canonical base pairings that form 12 geometric families. This offers a diverse set of structural and interacting motifs which allow for the construction of Nucleic Acid NanoParticles (NANPs). The versatile biochemistry of NANPs can be combined with the optical, electronic, and magnetic properties of inorganic nanomaterials. The further organization of these augmented NANPs into rationally designed supramolecular assemblies with controlled structural complexity can be used for application in biooptics, design of responsive devices, soft biomimetic machines, tissue mimics, and artificial muscles. Despite the existence of computational tools for NANP design, the use of NANPs as modular building blocks for supramolecular assemblies has never been systematically investigated. Therefore, this research program aims to address this gap in knowledge by developing a generalizable NANP-based programmable platform that simultaneously encodes targeted physicochemical, mechanical, and biological properties through networks of independently programmable architectural parameters. To achieve these goals, the team proposes three main objectives: (i) correlate the programmable parameters of NANPs with the physicochemical and mechanical properties of their supramolecular assemblies; (ii) evaluate the effect of functionalization of individual NANPs with inorganic nanomaterials on the physicochemical and mechanical properties of their supramolecular assemblies; and (iii) investigate the effect of stimuli-dependent kinetic pathways on the properties of functional supramolecular assemblies. This project will substantially advance the framework for the engineering of NANP supra-assemblies as novel stimuli-responsive materials and enable their use in a broad range of biomedical, electronic, and imaging applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.