DNAフレームワークベースの論理駆動型精密診断用分子トランスフォーマー
Shuyang Zhang1,2, Kai Xia3, Lihua Wang3,4
1Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Abstract:
Precision diagnostics requires logical integration of diverse biomarker information, but molecular heterogeneity and inconsistent identification kinetics hinder robust logic analysis. To overcome this, we develop a universal molecular transformer using DNA tetrahedral frameworks (DTFs) as programmable scaffolds. This system converts diverse biomarkers including proteins and variable-length nucleic acids into uniform 22-nucleotide DNA sequences, normalizing information dimensionality and identification kinetics. These uniform sequences serve as inputs for three fundamentals Boolean logic gates (AND, OR, and INHIBIT), enabling programmable molecular decision-making. Integrated on a gold-chip platform, the DTF transformer and logic system achieved statistically significant discrimination (P < 0.0001) among patients with prostate cancer, patients with benign prostatic hyperplasia, and healthy individuals using only two biomarkers (prostate-specific antigen and ALU115). By unifying signal transformation for Boolean logic computation, we resolve the critical challenges in molecular heterogeneity and establish a versatile platform for next-generation precision diagnostics.
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