Nanoparticle-based Artificial RNA Silencing Machine

非技术：该项目的总体目标是开发一类新的生物启发纳米材料（称为纳米酶或纳米机器人）。PI已经表明，这种纳米机器人技术补充了获得诺贝尔奖的基于rna的方法，并有可能成为基础生物医学研究的通用实验工具，以及对抗癌症和病毒感染等人类疾病的有效治疗工具。然而，由于使用弱结合野生型RNase A，目前纳米机器人的缺点大大减缓了它们在生物医学研究和应用中的应用。为了克服这个缺点，PI计划使用生物工程RNase A，它可以通过强大的多重化学键连接到金纳米粒子上，以构建新一代纳米机器人。未来三年，研究团队将通过优化DNA寡核苷酸序列和结构、RNase A的装载数量、金纳米颗粒的大小，系统地最大化纳米机器人的靶标选择性和酶促RNA裂解活性。这些拟议的研究工作将进一步与教育工作相结合，以培养多学科生物纳米技术研究领域的研究生和本科生，这对未来创造就业机会和国民经济增长很重要。教育工作还将包括对高中生的教育推广，重点是通过提高他们在地区和国际科学工程博览会上的竞争能力，提高他们对科学的兴趣。此外，佛罗里达大学的教育工作与美国国家科学基金会资助的教育项目（AGEP和REU）相结合。技术：该项目旨在开发一种新型的生物启发纳米材料（称为纳米酶）。他们的初步结果表明，这种纳米酶技术补充了基于RNAi （RNA干扰）的方法，并且有可能成为功能基因组学的通用实验工具和对抗癌症等人类疾病的有效治疗工具。然而，这些纳米酶是使用弱结合野生型RNase A制备的，这大大减缓了纳米酶在生物医学研究和应用中的使用。为了克服这个缺点，PI计划使用重组rna酶A，它将通过多个金-硫键连接到金纳米颗粒上，以构建新一代纳米酶。未来三年，课题组将通过系统优化DNA寡核苷酸的序列、结构和装载数量、RNase A装载数量、金纳米颗粒的大小，最大限度地提高纳米酶的靶向选择性和酶促RNA裂解活性。这些拟议的研究工作将进一步与教育工作结合起来。研究生和本科生将在拟议的多学科研究中接受培训。在这项研究的基础上，PI计划开发一款名为NanoBot的电脑游戏，作为教授本科生和研究生如何设计有效纳米酶的工具。此外，教育工作还包括向高中生推广，并与美国国家科学基金会资助的佛罗里达大学教育项目（AGEP和REU）相结合。该项目由材料研究部的生物材料项目和分子与细胞生物科学部的遗传机制项目共同资助。

Non-Technical: The general goal of this project is to develop a new class of bioinspired nanomaterials (called Nanozymes or nanorobots). The PI has shown that this nanorobot technology complements the Nobel Prize-winning RNAi-based methods and has the potential to become a general experimental tool for fundamental biomedical research and an effective therapeutic tool for combating human diseases such as cancers and viral infections. However, the drawback in the current nanorobots due to the use of weakly bound wild-type RNase A has substantially slowed down their use in biomedical research and applications. To overcome this drawback, the PI plans to use bioengineered RNase A, which can be attached onto gold nanoparticles with strong multiple chemical bonds to construct a new generation of nanorobots. The research team will systemically maximize the target selectivity and enzymatic RNA cleavage activity of nanorobots through optimizing the sequence and structure of DNA oligonucleotides, the loading number of RNase A, and the size of gold nanoparticles over the next three years. These proposed research efforts are further integrated with educational efforts for training graduate and undergraduate students in multidisciplinary bio-nanotechnology research areas, which is important for future job creation and national economic growth. The educational efforts will also include educational outreach for high school students, with a focus on promoting their interests in science by improving their competitive ability in regional and international science and engineering fairs. In addition, the educational efforts are integrated with NSF-funded education programs (AGEP and REU) at the University of Florida. Technical: This project aims to develop a new class of bioinspired nanomaterials (called Nanozymes). Their preliminary results have shown that this nanozyme technology complements the RNAi (RNA interference)-based methods and can potentially become a general experimental tool for functional genomics and an effective therapeutic tool for combating human diseases such as cancer. However, these nanozymes were prepared using weakly bound wild-type RNase A, which have substantially slowed down the nanozyme's use in biomedical research and applications. To overcome this drawback, the PI plans to use recombinant RNase A, which will be attached onto gold nanoparticles with multiple gold-sulfur bonds, to construct a new generation of nanozymes. The research team will maximize the target selectivity and enzymatic RNA cleavage activity of nanozymes through systemically optimizing the sequence, structure and loading number of DNA oligonucleotides, the loading number of RNase A, and the size of gold nanoparticles over the next three years. These proposed research efforts will be further integrated with educational efforts. Graduate and undergraduate students will be trained in the proposed multidisciplinary research. Based on the proposed research, the PI plans to create a computer game (called NanoBot) as a tool to teach undergraduate and graduate students how to design effective nanozymes. In addition, the educational efforts include outreach to high school students and are also integrated with NSF-funded education programs (AGEP and REU) at the University of Florida.This project is co-funded by the Biomaterials Program in the Division of Materials Research and the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.