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• W4385385648 abstract "DNA enzymes (DNAzymes) with site-specific RNA cleavage activity hold great promise as gene silencing agents, but more work is needed for these molecules to reach the clinic. The current best-in-class molecule is 10–23, a DNAzyme that advanced to phase I/II clinical trials. However, despite a promising safety profile, this DNAzyme fell short of expectations due to limited efficacy. Identifying variants that function with higher activity under physiological conditions where the concentration of free magnesium is low will no doubt challenge the minds of many nucleic acid chemists. One promising area of exploration is xeno-nucleic acids (XNAs), a large class of artificial genetic polymers having a novel sugar-phosphate backbone structure. XNAs have received considerable attention in recent years due to their unique physicochemical properties, which include enhanced biological stability and increased hybridization opposite complementary strands of RNA. In this chapter, we discuss XNAs as a possible route to chemically-modified DNAzymes that are capable of silencing the expression of disease-associated proteins. These molecules can be evolved de novo from large combinatorial libraries or generated by engineering a known DNAzyme scaffold, like 10–23. As these studies continue, it will be interesting to see how closely nucleic acid enzymes can approximate the activity of protein-driven gene silencing reagents." @default.
• W4385385648 created "2023-07-30" @default.
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• W4385385648 date "2023-01-01" @default.
• W4385385648 modified "2023-09-27" @default.
• W4385385648 title "Advancing XNAzymes as Nucleic Acid Therapeutics" @default.
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• W4385385648 doi "https://doi.org/10.1007/978-981-19-9776-1_75" @default.
• W4385385648 hasPublicationYear "2023" @default.
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