Engineered transcription factors (eTFs) binding diversed functional nucleic acids (dFNAs), as innovative biorecognition systems, have gradually become indispensable core elements for building synthetic biosensors. They not only circumvent the limitations of the original TF-based biosensing technologies, but also inject new vitality into the field of synthetic biosensing. This review aims to provide the first comprehensive and systematic dissection of the eTF-dFNA synthetic biosensor concept. Firstly, the core principles and interaction mechanisms of eTF-dFNA biosensors are clarified. Next, we elaborate on the construction strategies of eTF-dFNA synthetic biosensors, detailing methods for the personalized customization of eTFs (irrational design, rational design, and semi-rational design) and dFNAs (SELEX, modifying and predicting), along with the exploration of strategies for the flexible selection of signal amplification and output modes. Furthermore, we discuss the exceptional performance and substantial advantages of eTF-dFNA synthetic biosensors, analyzing them from four perspectives: recognition domain, detection speed, sensitivity, and construction methodology. Building upon this analysis, we present their outstanding applications in point-of-care diagnostics, food-safety detection, environmental monitoring, and production control. Finally, we address the current limitations of eTF-dFNA synthetic biosensors candidly and envision the future direction of this technology, aiming to provide valuable insights for further research and applications in this burgeoning field.

中文翻译：

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工程化转录因子结合多样化功能核酸基合成生物传感器


结合多样化功能核酸 （dFNA） 的工程转录因子 （eTFs） 作为创新的生物识别系统，已逐渐成为构建合成生物传感器不可或缺的核心元件。它们不仅规避了原有基于 TF 的生物传感技术的局限性，也为合成生物传感领域注入了新的活力。本文旨在首次全面、系统地剖析 eTF-dFNA 合成生物传感器概念。首先，阐明了 eTF-dFNA 生物传感器的核心原理和交互机制;接下来，我们详细阐述了 eTF-dFNA 合成生物传感器的构建策略，详细介绍了 eTFs （非理性设计、理性设计和半理性设计） 和 dFNA （SELEX， modifying and predicting） 的个性化定制方法，以及信号放大和输出模式灵活选择的策略探索。此外，我们讨论了 eTF-dFNA 合成生物传感器的卓越性能和实质性优势，从识别域、检测速度、灵敏度和构建方法四个角度对其进行了分析。在此分析的基础上，我们介绍了它们在即时诊断、食品安全检测、环境监测和生产控制方面的杰出应用。最后，我们坦率地解决了 eTF-dFNA 合成生物传感器的当前局限性，并设想了该技术的未来方向，旨在为这一新兴领域的进一步研究和应用提供有价值的见解。