Precise Disease Analysis and Diagnosis Driven by DNA Circuits: From Single Target to Multiple Targets, From Simple to Intelligent.

Medical decision-making and treatment efficacy depend fundamentally on accurate and early diagnosis. However, conventional diagnostic paradigms often face hurdles related to high invasiveness and a lack of molecular-level accuracy. To overcome these limitations, DNA circuits have flourished as a transformative technology, leveraging programmable dynamic DNA reaction networks to propel the field toward a new frontier of real-time intelligence and high-precision disease theranostics. In this review, we summarized the evolution of DNA circuits in disease diagnosis, with a focus on how they are becoming increasingly accurate, efficient, and intelligent. First, focusing on the input layer of DNA circuits, the evolution of detection targets from single target to multiple targets and multi-dimensional biomarkers was reviewed. Second, focusing on the core architecture of DNA circuits, we analyzed the architectural transition from simple logic gates to scalable and modular circuits that integrate algorithmic logic for intelligent diagnosis, signal amplification for low-abundance targets, and optimize circuit stability. Additionally, we surveyed recent developments in DNA circuits in disease diagnosis, analysis, and treatment. Finally, we discussed the remaining limitations and offer perspectives on the future of intelligent DNA circuits.