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• W4386413181 abstract "Altered by defects in p53, epigenetic silencing, and genomic loss, the microRNA miR-34a represents one of the most clinically relevant tumor-suppressive microRNAs. Without question, a striking number of patients with cancer would benefit from miR-34a replacement, if poor miR-34a stability, non-specific delivery, and delivery-associated toxicity could be overcome. Here, we highlight a fully modified version of miR-34a (FM-miR-34a) that overcomes these hurdles when conjugated to a synthetically simplistic ligand. FM-miR-34a is orders of magnitude more stable than a partially modified version, without compromising its activity, leading to stronger repression of a greater number of miR-34a targets. FM-miR-34a potently inhibited proliferation and invasion, and induced sustained downregulation of endogenous target genes for >120 h following in vivo delivery. In vivo targeting was achieved through conjugating FM-miR-34a to folate (FM-FolamiR-34a), which inhibited tumor growth leading to complete cures in some mice. These results have the ability to revitalize miR-34a as an anti-cancer agent, providing a strong rationale for clinical testing." @default.
• W4386413181 created "2023-09-05" @default.
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• W4386413181 date "2023-09-05" @default.
• W4386413181 modified "2023-10-14" @default.
• W4386413181 title "A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy" @default.
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• W4386413181 doi "https://doi.org/10.1038/s41388-023-02801-8" @default.
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• W4386413181 hasPublicationYear "2023" @default.
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