Leveraging Demethylase Activation in DNA Circuits to Overcome Signal Leakage for Reliable MicroRNA Bioimaging DOI
Yuchen Gao,

Mengdi Yu,

Jinhua Shang

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract DNA circuits show great potential in monitoring intracellular biomarkers based on their high programmability, predictability, and unique signal amplification capabilities, yet face challenges from uncontrollable leakage caused by the complex environment. Herein, a demethylase‐activated DNA‐assembly (DAD) circuit is designed for reliable robust imaging of cellular microRNA, incorporating sequential activation hybridization chain reaction (HCR) amplifier system. The DAD consists DNAzyme module microRNA‐recognizing HCR signal‐amplifying module. m 6 A‐modified sequence module, initially possessing temporally caged substrate‐cleavage activity, integrated into probe effectively blocking its miRNA‐sensing capacity. In presence ALKBH5 demethylase, methyl‐modifying unit removed, thus restoring catalytic substrate‐cleaving activity. This process exposed previously toehold region probe, thereby activating sensing miRNA. By leveraging activation, this can substantially enhance signal‐to‐background ratio, enabling highly sensitive miRNA detection efficient differentiation cancerous normal cells. Furthermore, established relationship between demethylase enzyme miRNA, paving way investigating more complicate biological processes intricate signaling pathways within

Language: Английский

Leveraging Demethylase Activation in DNA Circuits to Overcome Signal Leakage for Reliable MicroRNA Bioimaging DOI
Yuchen Gao,

Mengdi Yu,

Jinhua Shang

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract DNA circuits show great potential in monitoring intracellular biomarkers based on their high programmability, predictability, and unique signal amplification capabilities, yet face challenges from uncontrollable leakage caused by the complex environment. Herein, a demethylase‐activated DNA‐assembly (DAD) circuit is designed for reliable robust imaging of cellular microRNA, incorporating sequential activation hybridization chain reaction (HCR) amplifier system. The DAD consists DNAzyme module microRNA‐recognizing HCR signal‐amplifying module. m 6 A‐modified sequence module, initially possessing temporally caged substrate‐cleavage activity, integrated into probe effectively blocking its miRNA‐sensing capacity. In presence ALKBH5 demethylase, methyl‐modifying unit removed, thus restoring catalytic substrate‐cleaving activity. This process exposed previously toehold region probe, thereby activating sensing miRNA. By leveraging activation, this can substantially enhance signal‐to‐background ratio, enabling highly sensitive miRNA detection efficient differentiation cancerous normal cells. Furthermore, established relationship between demethylase enzyme miRNA, paving way investigating more complicate biological processes intricate signaling pathways within

Language: Английский

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