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.
Su-Jing Li, Sisi Wang, Yan-Bin Li et al.· Small· 0 citations
Severe neonatal-onset inborn errors of metabolism (IEMs), such as urea cycle disorders including carbamoyl phosphate synthetase 1 (CPS1) deficiency and the classic organic acidemias, present within days of birth with metabolic decompensation that carries high early mortality and, in survivors, a substantial burden of neurologic injury despite optimal medical management. Because most cases arise from defined point mutations, these disorders are conceptually well suited to one-time genetic correction. Base editing, which installs precise single-base changes without generating double-strand DNA breaks, and its companion technology, prime editing, have moved rapidly from laboratory description to in vivo demonstration in animals and, most recently, to a single human patient. In 2025, an infant with CPS1 deficiency ('KJ') received a bespoke lipid nanoparticle-delivered base-editing therapy designed and manufactured for that individual's specific variant, becoming the first reported recipient of a customized in vivo gene-editing medicine. This review synthesizes the clinical rationale for genetic correction of neonatal IEMs, the mechanistic basis and delivery strategies (lipid nanoparticles and adeno-associated virus) that make in vivo base editing feasible, and the preclinical evidence that preceded the first human case. We then examine the ethical dimensions of bespoke 'N-of-1' genetic medicine: the somatic versus germline distinction; consent for a non-autonomous neonate; equity, cost, and scalability; and the evolving regulatory pathway for individualized therapies. We conclude by distinguishing what has been proven in a single patient and in preclinical models from what remains speculative and by outlining what would need to generalize for a single case to become a platform.
O. Li, Yijiang Li, Su-Jing Li· Cureus· 0 citations