Scan and Unlock: A Programmable DNA Molecular Automaton for Cell-Selective Activation of Ligand-Based Signaling
Jinghui Zhang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorZongyang Qiu
Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Search for more papers by this authorJiahui Fan
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorFang He
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorWenyuan Kang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorSihui Yang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Hong-Hui Wang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Jing Huang
Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Zhou Nie
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorJinghui Zhang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorZongyang Qiu
Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Search for more papers by this authorJiahui Fan
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorFang He
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorWenyuan Kang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorSihui Yang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Hong-Hui Wang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Jing Huang
Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences Westlake University, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Zhou Nie
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082 P. R. China
Search for more papers by this authorDedicated to the 100th anniversary of chemistry at Nankai University.
Abstract
Selective modulation of ligand–receptor interaction is essential in targeted therapy. In this study, we design an intelligent “scan and unlock” DNA automaton (SUDA) system to equip a native protein-ligand with cell-identity recognition and receptor-mediated signaling in a cell-type-specific manner. Using embedded DNA-based chemical reaction networks (CRNs) on the cell surface, SUDA scans and evaluates molecular profiles of cell-surface proteins via Boolean logic circuits. Therefore, it achieves cell-specific signal modulation by quickly unlocking the protein-ligand in proximity to the target cell-surface to activate its cognate receptor. As a proof of concept, we non-genetically engineered hepatic growth factor (HGF) with distinct logic SUDAs to elicit target cell-specific HGF signaling and wound healing behaviors in multiple heterogeneous cell types. Furthermore, the versatility of the SUDA strategy was shown by engineering tumor necrotic factor-α (TNFα) to induce programmed cell death of target cell subpopulations through cell-specific modulation of TNFR1 signaling.
Conflict of interest
The authors declare no conflict of interest.
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