Abstract：Nucleic acids have emerged as powerful and functional materials due to their ability to achieve precise hybridization between nucleic acids and molecular recognition toward a wide range of targets. Despite the promise, their applications are still limited. In this seminar, I will present two examples that demonstrate innovations in experimental designs have overcome the limitations and resulted in wider applications. First, utilizing the property of precise molecular recognition, I have designed a riboswitch sensor for on-site and real-time detection of fluoride. Specifically, current portable fluoride sensors are limited by their poor performance in aqueous solutions, such as low selectivity, sensitivity, and narrow dynamic range. To overcome these limitations, I coupled a fluoride riboswitch-regulated transcription with CRISPR-Cas13-based signal amplification, allowing quantitative detection of fluoride in aqueous solutions with high sensitivity, high selectivity, and a wide dynamic range. This work has also expanded the application of nucleic acid sensors from cations and neutral molecules to anions. Second, utilizing both properties of precise hybridization and molecular recognition, I have developed a nucleic acid-based bioimaging tool to investigate glycoRNA biology. While glycosylated RNAs (glycoRNAs) have recently been discovered as a new class of glycosylated biomolecules, our understanding of their roles is limited because of a lack of visualization methods. To overcome this limitation, I developed the first spatial imaging method to visualize glycoRNAs in cells with high sensitivity and selectivity. Using this method, we discovered spatial distributions of glycoRNAs on lipid rafts and cell trafficking through SNARE protein-mediated secretory exocytosis. We found that surface glycoRNAs are inversely associated with tumor malignancy and metastasis and that glycoRNAs may mediate cell-cell interactions during the immune response. This work has expanded the toolbox for glycoRNA research, paving the way for exploring the roles of glycoRNAs in diverse biological processes. Together, the two examples demonstrate that innovations in developing nucleic acid-based tools can result in better sensors for anions, and a deeper understanding of glycoRNAs in biology and diseases.