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• W3141674590 abstract "The potential therapeutic and diagnostic applications of oligonucleotides have attracted great attention. However, natural antisense oligonucleotides (ASONs) are susceptible to degradation by intracellular and extracellular nucleases. In this study, we developed a new class of prodrug-type ASONs, which typically bear the hairpin-end conformation with a responsive disulphide switch. The hairpin-end conformation provides protection against nuclease degradation, and, upon stimulation, the molecule converts into the native antisense structure upon entering a tumour microenvironment due to the high concentration of glutathione. The structure-stability relationship analysis indicated that the location, size and composition of the hairpin structure affect the anti-degradation capability. One optimal prodrug-type ASON, O2, exhibited a higher stability against nucleases in serum-containing medium as well as an increased anti-tumour activity both in vitro and in vivo, compared to the linear control. This work presents a new strategy for the design of ASON drugs with novel structures and offers insight on the stability and biological efficacy of general nucleic acid-based therapeutics." @default.
• W3141674590 created "2021-04-13" @default.
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• W3141674590 date "2021-07-01" @default.
• W3141674590 modified "2023-09-29" @default.
• W3141674590 title "Prodrug-type antisense oligonucleotides with enhanced nuclease stability and anti-tumour effects" @default.
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• W3141674590 doi "https://doi.org/10.1016/j.ejps.2021.105832" @default.
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