Valency-Controlled Framework Nucleic Acid Signal Amplifiers

Qi Liu; Zhilei Ge; Xiuhai Mao; Guobao Zhou; Xiaolei Zuo; Juwen Shen; Jiye Shi; Jiang Li; Lihua Wang; Xiaoqing Chen; Chunhai Fan

doi:10.1002/anie.201802701

Valency-Controlled Framework Nucleic Acid Signal Amplifiers

Angew Chem Int Ed Engl. 2018 Jun 11;57(24):7131-7135. doi: 10.1002/anie.201802701. Epub 2018 Apr 19.

Authors

Qi Liu^{1

2}, Zhilei Ge³, Xiuhai Mao¹, Guobao Zhou³, Xiaolei Zuo¹, Juwen Shen⁴, Jiye Shi⁵, Jiang Li³, Lihua Wang³, Xiaoqing Chen², Chunhai Fan³

Affiliations

¹ Institute of Molecular Medicine, Renji Hospital, School of Medicine and School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China.
² College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China.
³ Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
⁴ Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
⁵ UCB Pharma, Slough, SL1 3WE, UK.

PMID: 29603524
DOI: 10.1002/anie.201802701

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: DNA nanostructure; biosensors; cfDNA; framework nucleic acids; valence-engineering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biosensing Techniques / methods*
DNA, Circular / analysis*
Electrochemical Techniques / methods
Limit of Detection
Nanostructures / chemistry*
Nucleic Acid Amplification Techniques / methods
Nucleic Acids / chemistry*

Substances

DNA, Circular
Nucleic Acids