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Scan and Unlock: A Programmable DNA Molecular Automaton for Cell‐Selective Activation of Ligand‐Based Signaling
Author(s) -
Zhang Jinghui,
Qiu Zongyang,
Fan Jiahui,
He Fang,
Kang Wenyuan,
Yang Sihui,
Wang HongHui,
Huang Jing,
Nie Zhou
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202015129
Subject(s) - ligand (biochemistry) , cell , microbiology and biotechnology , signal transduction , receptor , chemistry , biology , biochemistry
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.