生物标志物已成为医学研究热点。转录因子(TFs)是潜在的诊断标志物和药物研究靶标, 但由于分析手段仍存在较大缺陷, 极大影响了其作为临床分子诊断靶标的应用。本课题组将在前期纳米传感技术研究与应用基础上, 以TFs为代表性靶标，基于DNA-AgNCs构建可控分子自组装新型分子信标（AgMBs），设计应用酶辅信号放大技术，通过将TFs结合信号转化为核酸分子信号（reporter）方式，探索研究用于检测低丰度TFs的荧光传感系统，从而克服以往TFs检测技术无法同时满足低成本、高选择性、高灵敏度的缺点。本课题组通过初步合成的AgMBs，采用凝胶电泳法对传感系统各关键步骤的预试验已表明本方案的可行性(详见研究基础的预试验结果)。本项目不仅将为生物标志物研究与临床分子诊断提供一种集分子识别、信号放大和荧光传感为一体的分析系统，而且将为新药筛选及基础医学研究创立新型分析手段。

Biomarker is a hot issue in biomedical research. As a potential diagnostic marker and therapeutic target, transcription factors (TFs) is a significant target in both basic and clinical medicine. However, present assays for TFs detection are facing various drawbacks, which greatly hinders the application of TFs as a biomarker. Herein, based on the previous study and investigation in nano-sensing, our group developed a fluorescent sensing system for detecting low-abundance TFs using DNA-silver nanocluster molecular beacons (AgMBs) which is a novel molecular beacon with controllable molecular self-assembly. By integrating the AgMBs and enzyme-assisted signal amplification strategy, TFs binding signal was translated into a nucleic acid molecular signal (reporter). This detection system can realize cost-effective, highly selective and sensitive detection of TFs which is rarely achieved in previous reports. We first synthesized AgMBs, then monitoring several key procedure of sensing system by gel electrophoresis to confirm the feasibility of this sensing route (detailed in results of trial tests in basic research). This project will not only provide a new analytic system combined molecular recognition, signal amplification and fluorescent sensing for biomarker researches and clinical molecular diagnoses, but also establish a new analytical method for drug screening and biomedical research.