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A Master-Key DNA System Enabling Programmable Cross-Talks in Biomimetic Networks via An Artificial Chaperone

Preprint Created on 18 Jun 2026 bioRxiv

Biological systems operate through complex molecular networks programmed by genetic information; however, constructing artificial systems with multilayered control remains a significant challenge. Here, we report a simple and integrated master-key system governed by lock DNA and master key DNA, reversibly switching diverse downstream processes ON/OFF and achieving dynamic cross-talks among distinct molecular components. The system utilizes cationic copolymer chaperones as control nodes, based on poly(L-lysine) or poly(allylamine) grafted with hydrophilic side chains, with a peptide nucleic acid (PNA) plug-in that grants sequence-specificity. We demonstrated two proof-of-concept systems: a nucleic acid-based catalytic network responsive to microRNA let-7b and a peptide-mediated transformation of lipid bilayers from two-dimensional sheets to three-dimensional vesicles. Both systems exhibited precise, modular, and programmable control with high robustness, mimicking the governing role of nucleic acids in biological systems. This strategy provides a versatile design framework for constructing biomimetic molecular networks and studying biological systems.

Zhang, W., Saito, M., Fujii, K., Shimada, N., Maruyama, A.

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