Journal
NANO LETTERS
Volume 22, Issue 1, Pages 347-354Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c03969
Keywords
CpG methylation; G-quadruplex DNAzyme nanowire; in situ assembling nanodevice; one-step detection; disease diagnosis
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Funding
- National Natural Science Foundation of China [21735003]
- Award for Team Leader Program of Taishan Scholars of Shandong Province, China
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A nanodevice for one-step detection of CpG methylation with high specificity and sensitivity was demonstrated, capable of detecting very low methylation levels in vitro and distinguishing methylation levels in different tumor cells in vivo.
CpG methylation is one the most predominant epigenetic modification that has been recognized as a molecular-level biomarker for various human diseases. Taking advantage of methylation-dependent cleavage and encoding flexibility in nucleic acid functions and structures, we demonstrate the cooperative in situ assembly of G-quadruplex DNAzyme nanowires for one-step sensing of CpG methylation in human genomes. This nanodevice displays good specificity and high sensitivity with a limit of detection (LOD) of 0.565 aM in vitro and 1 cell in vivo. It can distinguish 0.001% CpG methylation level from excess unmethylated DNA, quantify different CpG methylation targets from diverse human cancer cells, and even discriminate CpG methylation expressions between lung tumor and precancerous tissues. Importantly, this nanodevice can be performed isothermally in one step within 2 h in a label-free manner without any bisulfite conversion, fluorescence tagging, and PCR amplification process, providing a new platform for genomic methylation-related clinical diagnosis and biomedical research.
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