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，他建议化学合成基于小分子的细胞渗透性RNA传感器，当与特定的RNA结合时，这种传感器会发光。化学合成简明扼要，易于调节灵敏度和特异度。以前，人们认为必须合成一个候选RNA化学传感器文库，并针对特定的RNA进行筛选。然而，要合理地设计特定的RNA配体和费力地化学合成一个小分子文库是极其困难的。这项拟议的研究的意义在于，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，在合成有机化学的帮助下设计特定的RNA-小分子相互作用。这种RNA传感器开发的反向范式具有很高的创新性，将对其他人如何设计实验来开发其他RNA传感器产生重大影响。由于缺乏探针，人们对活细胞中的RNA生物学知之甚少。这项研究的重点是开发仅在与特定RNA结合时才会发光的化学传感器。这种方法是基于合理设计和基于库的发现相结合的。这项研究的结果将对生物成像和DNA转录生物学产生广泛影响。Koide教授的研究可能会对化学、生物学、制药业和普通公众产生重大影响。这个项目将培养学生和博士后研究员成为科学家，他们将能够弥合化学和生物学之间的差距。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，该项目将为这些领域培养训练有素的科学家。通过这个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努力。

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.