Fluorescent Sensors to Image RNA

美国国家科学基金会化学部的有机和大分子化学项目支持匹兹堡大学的Kazunori Koide教授，他提出化学合成基于小分子的细胞可渗透RNA传感器，当与特定RNA结合时会发出荧光。化学合成是简洁的，并且易于调节灵敏度和特异性。以前，人们认为RNA化学传感器候选物的文库必须合成并针对特定RNA进行筛选。然而，合理地设计特异性RNA配体是极其困难的，并且化学合成小分子文库是费力的。这项拟议研究的意义在于，人们不需要创建RNA配体来开发RNA化学传感器;相反，拟议的研究将利用成熟的体外RNA选择作为一种手段，在合成有机化学的一些帮助下设计特定的RNA-小分子相互作用。这种反向的RNA传感器开发范式具有高度的创新性，将对其他人如何设计实验以开发其他RNA传感器产生重大影响。由于缺乏探针，对活细胞中RNA的生物学知之甚少。这项研究的重点是开发仅在与特定RNA结合时才发出荧光的化学传感器。该方法是基于合理的设计和基于库的发现相结合。这项研究的结果将对生物成像和DNA转录生物学产生广泛的影响。小出教授的研究可能会对化学，生物学，制药业和公众产生重大影响。该项目将培养学生和博士后研究员成为能够弥合化学和生物学之间差距的科学家。制药和生物技术公司的领导者需要这两个领域的知识来发明药物或诊断工具，本项目将为此培养训练有素的科学家。通过本研究项目培训的学生将了解合成，分析和光谱化学以及生物学，并将能够从事处于科学前沿的多学科工作。

The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Kazunori Koide of the University of Pittsburgh who proposes to chemically synthesize small molecule-based cell-permeable RNA sensors that fluoresce when bound to specific RNA. Chemical synthesis is concise and amenable to tuning sensitivity and specificity. Previously, it was thought that a library of RNA chemosensor candidates must be synthesized and screened against specific RNA. However, it is exceedingly difficult to rationally design specific RNA ligands and strenuous to chemically synthesize a library of small molecules. The significance of this proposed research is that one does not need to create RNA ligands to develop RNA chemosensors; rather, the proposed research will take advantage of well-established in vitro RNA selection as a means to engineer specific RNA-small molecule interaction with some help from synthetic organic chemistry. This reversed paradigm for RNA sensor development is highly innovative and will have significant impact on how others will design experiments to develop other RNA sensors. The biology of RNA in live cells is poorly understood due to the lack of probes. This research focuses on developing chemosensors that fluoresce only when bound to specific RNA. The approach is based on the combination of rational design and library-based discovery. The outcome of this study will have broad impact on bioimaging and the biology of DNA transcription.Research by Professor Koide could significantly impact chemistry, biology, the pharmaceutical industry, and the general public. This project will train students and postdoctoral fellows to become scientists who will be able to bridge the gap between chemistry and biology. Leaders in pharmaceutical and biotechnology companies require knowledge in both fields to invent drugs or diagnostic tools, for which this project will produce well-trained scientists. Students trained by this research project will understand synthetic, analytical, and spectroscopic chemistry as well as biology, and will be able to be engaged in multidisciplinary efforts that are at the forefront of science.