An Intelligent Allosteric DNAzyme Platform for On-Site Uracil-DNA Glycosylase Imaging and On-Demand Gene Regulation

Le résumé fourni par la source

High Resolution Image Download MS PowerPoint Slide Uracil DNA glycosylase (UDG) is a crucial DNA repair enzyme involved in maintaining genomic stability. Precise monitoring of UDG facilitates in-depth elucidation of DNA repair and the onset and progression mechanisms of diseases. However, conventional UDG sensing approaches suffer from low accuracy and off-target signal leakage, limiting their applicability for precise in situ imaging and functional studies. Here, we report a UDG-activated allosteric DNAzyme (UAZ) platform that leverages an intramolecular recognition–allosteric–amplification strategy to achieve high-fidelity UDG detection and programmable gene regulation. In this design, the UDG-responsive uracil residue is introduced to disrupt the catalytic structure of DNAzyme and make DNAzyme inactive. Upon specific uracil excision by UDG, the precise allosteric reconfiguration restores the catalytic activity of DNAzyme, enabling efficient substrate cleavage and amplified fluorescence output. This mechanism eliminates off-target activation, realizing reliability and high-contrast UDG imaging. Furthermore, the modular UAZ platform was reprogrammed into a gene-silencing variant (gsUAZ) for selectively downregulating survivin mRNA in UDG-overexpressing cancer cells, thereby inducing cancer cell apoptosis with minimal effects on normal cells, ultimately realizing targeted gene therapy. This multifunctional UAZ system thus serves as both a sensitive molecular imaging tool and a targeted gene therapy agent, offering a versatile toolbox for disease diagnosis and precision gene therapy.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.