Scan and Unlock: A Programmable DNA Molecular Automaton for Cell‐Selective Activation of Ligand‐Based Signaling. Issue 12 (12th February 2021) - Zhang, Jinghui
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. Abstract : An intelligent molecular‐lock device of signaling ligand proteins, termed "scan and unlock" DNA automaton (SUDA), is presented. The SUDA employs DNA chemical reaction networks to autonomously scan and logically evaluate the cell‐surface‐protein profile of the designated cell type, selectively unlocking the signaling ligand–receptor interactions for cell‐specific signaling.