Self-resetting molecular probes for nucleic acids detection enabled by fuel dissipative systems

Na Li; Yuee Zhao; Yu Liu; Zhe Yin; Rui Liu; Linghao Zhang; Liang Ma; Xiaochuan Dai; Dongsheng Zhou; Xin Su

doi:10.1016/j.nantod.2021.101308

Self-resetting molecular probes for nucleic acids detection enabled by fuel dissipative systems

Nano Today. 2021 Dec:41:101308. doi: 10.1016/j.nantod.2021.101308. Epub 2021 Oct 2.

Authors

Na Li¹, Yuee Zhao², Yu Liu¹, Zhe Yin², Rui Liu³, Linghao Zhang¹, Liang Ma⁴, Xiaochuan Dai³, Dongsheng Zhou², Xin Su¹

Affiliations

¹ College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
² State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
³ Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
⁴ Clinical Laboratory, China-Japan Friendship Hospital, Beijing 100029, China.

Abstract

A once-in-a-century global public health crisis, the COVID-19 pandemic has damaged human health and world economy greatly. To help combat the virus, we report a self-resetting molecular probe capable of repeatedly detecting SARS-CoV-2 RNA, developed by orchestrating a fuel dissipative system via DNA nanotechnology. A set of simulation toolkits was utilized to design the probe, permitting highly consistent signal amplitudes across cyclic detections. Uniquely, full width at half maximum regulated by dissipative kinetics exhibits a fingerprint signal suitable for high confidential identifications of single-nucleotide variants. Further examination on multiple human-infectious RNA viruses, including ZIKV, MERS-CoV, and SARS-CoV, demonstrates the generic detection capability and superior orthogonality of the probe. It also correctly classified all the clinical samples from 55 COVID-19 patients and 55 controls. Greatly enhancing the screening capability for COVID-19 and other infectious diseases, this probe could help with disease control and build a broader global public health agenda.

Keywords: COVID-19; DNA nanotechnology; Exonuclease III; Fuel dissipation; Kinetic simulation; MD simulation; SARS-CoV-2; Toehold mediated strand displacement.