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Valency‐Controlled Framework Nucleic Acid Signal Amplifiers
Authors:Dr. Qi Liu  Dr. Zhilei Ge  Dr. Xiuhai Mao  Dr. Guobao Zhou  Prof. Xiaolei Zuo  Dr. Juwen Shen  Dr. Jiye Shi  Prof. Jiang Li  Prof. Lihua Wang  Prof. Xiaoqing Chen  Prof. Chunhai Fan
Affiliation:1. Institute of Molecular Medicine, Renji Hospital, School of Medicine and School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China;2. College of Chemistry and Chemical Engineering, Central South University, Changsha, China;3. Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China;4. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China;5. UCB Pharma, Slough, UK
Abstract:Weak ligand–receptor recognition events are often amplified by recruiting multiple regulatory biomolecules to the action site in biological systems. However, signal amplification in in vitro biomimetic systems generally lack the spatiotemporal regulation in vivo. Herein we report a framework nucleic acid (FNA)‐programmed strategy to develop valence‐controlled signal amplifiers with high modularity for ultrasensitive biosensing. We demonstrated that the FNA‐programmed signal amplifiers could recruit nucleic acids, proteins, and inorganic nanoparticles in a stoichiometric manner. The valence‐controlled signal amplifier enhanced the quantification ability of electrochemical biosensors, and enabled ultrasensitive detection of tumor‐relevant circulating free DNA (cfDNA) with sensitivity enhancement of 3–5 orders of magnitude and improved dynamic range.
Keywords:biosensors  cfDNA  DNA nanostructure  framework nucleic acids  valence-engineering
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