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Target-activated transcription for the amplified sensing of protease biomarkers

Abstract

Signal amplification is an effective way to achieve sensitive analysis of biomarkers, exhibiting great promise in biomedical research and clinical diagnosis. Inspired by the transcription process, we here present a versatile strategy that enables to effectively amplify proteolysis into nucleic acid signal outputs in homogeneous system. In this strategy, a protease-activatable T7 RNA polymerase is engineered as the signal amplifier, which achieves 3 orders of magnitude amplification in signal gain. The versatility of this strategy has been demonstrated in the development of sensitive and selective assays for protease biomarkers, such as matrix metalloproteinase-2 (MMP-2) and thrombin with sub-picomole sensitivity, which is 4.3 × 103-fold lower than that of the standard peptide-based method. Moreover, the proposed assay has been further applied in the detection of MMP-2 secreted by cancer cells, as well as in the assessment of MMP-2 levels in osteosarcoma tissue samples, providing a general approach for the monitoring of protease biomarkers in clinical diagnosis.

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Supplementary files

Article information


Submitted
18 Sep 2019
Accepted
09 Feb 2020
First published
10 Feb 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020, Accepted Manuscript
Article type
Edge Article

Target-activated transcription for the amplified sensing of protease biomarkers

F. Liu, M. Yang, W. Song, X. Luo, R. Tang, Z. Duan, W. Kang, S. Xie, Q. Liu, C. Lei, Y. Huang, Z. Nie and S. Yao, Chem. Sci., 2020, Accepted Manuscript , DOI: 10.1039/C9SC04692E

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