Wen Mei, Huang Zhaoxin, Yin Yao, Wang Yin, Wang Menghui, Huang Xueyuan, Chen Ting, Ke Guoliang, Chen Mei, Zhang Xiao-Bing
College of Materials Science and Engineering, College of Chemistry and Chemical Engineering, State Key Laboratory for Chemo/Biosensing and Chemometrics, Hunan University, Changsha, Hunan, 410082, China.
Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410083, China.
Talanta. 2025 Feb 1;283:127078. doi: 10.1016/j.talanta.2024.127078. Epub 2024 Oct 23.
Mature microRNAs play crucial roles in tumorigenesis and progression. However, their potential as cancer biomarkers is limited by the sequence interference of precursor microRNAs and the occurrence of false positive signals mediated by single microRNAs. Herein, we reported a dual mature microRNA-responsive second-order (YES-AND) logic biosensing platform for accurate cancer diagnosis. Specifically, DNA nanocages were conceived as the first stage of "YES" gates, capable of signal transduction through strand displacement reactions, and realizing size-selective discrimination of mature microRNAs and pre-microRNAs. Subsequently, CRISPR/Cas12a system served as the second stage of "AND" gate, wherein dual activators cooperatively triggered trans-cleavage. As a proof-of-concept, this second-order logic biosensing platform was successfully applied to detect non-small cell lung cancer-related mature microRNA in clinical serum, and showed remarkable sensitivity (Lod = 100 pM) and trueness (recovery ≥90 %). Our study represents a significant step forward in the development of intelligent biosensors capable of performing complex computations within pathological networks, and opens up broader possibilities for applications in biological science study and clinic disease diagnosis.
成熟的微小RNA在肿瘤发生和进展中发挥着关键作用。然而，它们作为癌症生物标志物的潜力受到前体微小RNA的序列干扰以及单个微小RNA介导的假阳性信号出现的限制。在此，我们报道了一种用于准确癌症诊断的双成熟微小RNA响应二阶（“是且”）逻辑生物传感平台。具体而言，DNA纳米笼被设计为“是”门的第一阶段，能够通过链置换反应进行信号转导，并实现对成熟微小RNA和前体微小RNA的尺寸选择性区分。随后，CRISPR/Cas12a系统作为“与”门的第二阶段，其中双激活剂协同触发反式切割。作为概念验证，该二阶逻辑生物传感平台成功应用于检测临床血清中与非小细胞肺癌相关的成熟微小RNA，并显示出显著的灵敏度（检测限=100 pM）和准确性（回收率≥90%）。我们的研究代表了在能够在病理网络内执行复杂计算的智能生物传感器开发方面向前迈出的重要一步，并为生物科学研究和临床疾病诊断中的应用开辟了更广阔的可能性。
