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On gene silencing by the X10-23 DNAzyme

NATURE CHEMISTRY (2022)

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Summary: DNAzymes are single-stranded DNA molecules that catalyze a broad range of chemical reactions, with the 10-23 DNAzyme being particularly effective at cleaving RNA strands. The influence of monovalent and divalent cations on the DNAzyme's activity was studied, showing that they affect the binding of metal ions to the DNAzyme:RNA complex and modulate the reaction rates of RNA cleavage. High levels of Na+ and K+ concentrations were found to have an opposite effect on Mg2+ - and Mn2+-induced reactions, revealing a different interplay of these metals in catalysis.

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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A biologically stable DNAzyme that efficiently silences gene expression in cells

Yajun Wang et al.

Summary: Efforts to use RNA-cleaving DNA enzymes as gene-silencing agents have been hindered by low efficacy in clinical trials, but a new xeno-nucleic-acid-modified DNAzyme called X10-23 has shown promise in achieving multiple-turnover activity and resisting nuclease digestion in cellular conditions. X10-23 overcomes product inhibition and facilitates persistent gene silencing in mammalian cells, suggesting new molecular chemotypes can enhance the activity and stability of DNAzymes for potential therapeutic applications.

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Structural Rearrangements of the 10-23 DNAzyme to β3 integrin subunit mRNA induced by cations and their relations to the catalytic activity

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E Yang et al.

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