Self-Adaptive Activation of DNAzyme Nanoassembly for Synergistically Combined Gene Therapy.
Autor: | Wang J; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China.; College of Health Science and Engineering, Key Laboratory for the Synthesis and Application of Organic Functional Molecules (Ministry of Education), Hubei University, 430062, Wuhan, P. R. China., Shang J; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China., Yu S; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China., Lin M; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China., Gong X; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China., Liu X; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China., Liu Z; College of Health Science and Engineering, Key Laboratory for the Synthesis and Application of Organic Functional Molecules (Ministry of Education), Hubei University, 430062, Wuhan, P. R. China., Wang F; College of Chemistry and Molecular Sciences, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan University, 430072, Wuhan, P. R. China. |
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Jazyk: | angličtina |
Zdroj: | Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Oct 16, pp. e202417363. Date of Electronic Publication: 2024 Oct 16. |
DOI: | 10.1002/anie.202417363 |
Abstrakt: | DNAzyme represents a promising gene silencing toolbox yet is obstructed by the poor substrate accessibility in specific cells. Herein, a compact DNA nanoassembly, incorporating multimeric therapeutic DNAzyme, was prepared for selective delivery of gene-silencing DNAzyme with requisite cofactors and auxiliary chemo-drugs. By virtue of the sequence-conservative duplex-specific nuclease, the endogenous miRNA catalyzes the successive and site-specific cleavage of DNA nanoassembly substrate (nominated as the localized RNA walking machine) and thus ensures the liberation/activation of therapeutic agents with high accuracy and efficacy. The miR-10b-stimulated DNAzyme was designed to downregulate the TWIST transcription factor, an upstream promotor of miR-10b, thus acquiring the self-sufficient downregulation of TWIST/miR-10b signaling nodes (self-adaptive negative feedback loop) for abrogating tumor metastasis and chemo-resistance issues. (© 2024 Wiley-VCH GmbH.) |
Databáze: | MEDLINE |
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