Accessible and adaptable nucleic acid diagnostics remains a critical challenge in managing the evolving COVID-19 pandemic. Here, an integrated molecular nanotechnology that enables direct and programmable detection of SARS-CoV-2 RNA targets in native patient specimens is reported. Termed synergistic coupling of responsive equilibrium in enzymatic network (SCREEN), the technology leverages tunable, catalytic molecular nanostructures to establish an interconnected, collaborative architecture. SCREEN mimics the extraordinary organization and functionality of cellular signaling cascades. Through programmable enzyme–DNA nanostructures, SCREEN activates upon interaction with different RNA targets to initiate multi-enzyme catalysis; through system-wide favorable equilibrium shifting, SCREEN directly transduces a single target binding into an amplified electrical signal. To establish collaborative equilibrium coupling in the architecture, a computational model that simulates all reactions to predict overall performance and optimize assay configuration is developed. The developed platform achieves direct and sensitive RNA detection (approaching single-copy detection), fast response (assay reaction is completed within 30 min at room temperature), and robust programmability (across different genetic loci of SARS-CoV-2). When clinically evaluated, the technology demonstrates robust and direct detection in clinical swab lysates to accurately diagnose COVID-19 patients.

中文翻译：

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催化 DNA 纳米结构的协同平衡偶联可实现 SARS-CoV-2 的可编程检测

易于获取且适应性强的核酸诊断仍然是管理不断演变的 COVID-19 大流行的关键挑战。本文报道了一种集成分子纳米技术，可以直接、可编程地检测本地患者样本中的 SARS-CoV-2 RNA 靶标。该技术被称为酶网络中响应平衡的协同耦合（SCREEN），利用可调节的催化分子纳米结构来建立一个互连的协作架构。SCREEN 模仿细胞信号级联的非凡组织和功能。通过可编程酶-DNA纳米结构，SCREEN在与不同RNA靶标相互作用时激活，启动多酶催化；通过全系统有利的平衡转移，SCREEN 直接将单个靶标结合转换成放大的电信号。为了在架构中建立协作平衡耦合，开发了一个模拟所有反应以预测整体性能并优化测定配置的计算模型。开发的平台实现了直接灵敏的RNA检测（接近单拷贝检测）、快速响应（室温下30分钟内完成检测反应）和强大的可编程性（跨越SARS-CoV-2的不同基因位点）。在临床评估中，该技术证明了对临床拭子裂解物的稳健和直接检测，可以准确诊断 COVID-19 患者。