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| Main Authors: | , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of medicinal chemistry
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39921644/ |
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Table of Contents:
- NQO1-Activatable Circular Antisense Oligonucleotides for Tumor-Cell-Specific Survivin Gene Silencing and Antitumor Therapy. Zhao, Xiaoran Xu, Jianfei Liang, Xingxing Wang, Zhongyu Zhu, Yuejie Guo, Dongyang Wang, Jing Amu, Gubu Wang, Qian Yang, Zhenjun Tang, Xinjing Humans NAD(P)H Dehydrogenase (Quinone) Survivin Oligonucleotides, Antisense Gene Silencing Animals Antineoplastic Agents Mice Mice, Nude Cell Line, Tumor Mice, Inbred BALB C Lung Neoplasms NAD(P)H:quinone oxidoreductase-1 (NQO1), a protein highly expressed in tumor cells, serves as an excellent trigger for releasing drugs specifically within tumor cells. In this study, we designed an activatable circular antisense oligonucleotide (cASO) by incorporating a head-to-tail cyclization mediated by an NQO1-responsive trimethyl-locked quinone propionate (Q3PA), coupled with a self-immolative linker. The resulting circular structure prevented the cASO from binding to the target mRNA, thereby avoiding gene silencing. However, upon encountering NQO1, the circular form was converted to a linear form, leading to the silencing of the targeted gene. experiments demonstrated significant tumor-cell-specific activity of the cASO, while studies using an A549-Luc orthotopic lung tumor model revealed a substantial antitumor effect, primarily attributed to the suppression of survivin expression. This NQO1-activatable cASO represents a novel strategy for achieving tumor-cell-specific gene silencing and holds promise for the development of ASO prodrugs with enhanced therapeutic potentials.