10/31/2023 0 Comments Nucleic acid backboneTargeting insulin-like growth factor I with 10–23 DNAzymes: 2′-O-methyl modifications in the catalytic core enhance mRNA cleavage. RNA cleaving ‘10–23′ DNAzymes with enhanced stability and activity. Inhibition of respiratory syncytial virus in cultured cells by nucleocapsid gene targeted deoxyribozyme (DNAzyme). DNAzyme-mediated inhibition of Japanese encephalitis virus replication in mouse brain. Mechanism and utility of an RNA-cleaving DNA enzyme. The chemical evolution of oligonucleotide therapies of clinical utility. A general purpose RNA-cleaving DNA enzyme. Together, these results demonstrate that new molecular chemotypes can improve the activity and stability of DNAzymes, and may provide a new route for nucleic acid enzymes to reach the clinic. ![]() In cultured mammalian cells, X10–23 facilitates persistent gene silencing by efficiently degrading exogenous and endogenous messenger RNA transcripts. ![]() ![]() The new reagent, X10–23, overcomes the problem of product inhibition, which limited previous 10–23 designs, using molecular chemotypes with DNA, 2′-fluoroarabino nucleic acid and α- l-threofuranosyl nucleic acid backbone architectures that balance the effects of enhanced biological stability with RNA hybridization and divalent metal ion coordination. Here we report a xeno-nucleic-acid-modified version of the classic DNAzyme 10–23 that achieves multiple-turnover activity under cellular conditions and resists nuclease digestion. Efforts to use RNA-cleaving DNA enzymes (DNAzymes) as gene-silencing agents in therapeutic applications have stalled due to their low efficacy in clinical trials.
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