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• W2914686093 startingPage "427" @default.
• W2914686093 abstract "Autophagy and endocytosis are important pathways regulating macromolecule recycling and regeneration. Small molecule inhibitors are utilized to modulate these pathways and to treat autophagy-related diseases. Vacuolin-1 is a small molecule that can potently and reversibly inhibit autophagy by activating Rab5. In addition, Vacuolin-1 can be applied to inhibit exocytosis in a variety of cell types. Here we report that Vacuolin-1 significantly reduces small interference RNA (siRNA)-mediated gene silencing delivered by liposome transfection reagent or lipid nanoparticles in Hela cells. Vacuolin-1 exhibits the strongest inhibition effect among a few autophagy inhibitors including Chloroquine, Wortmannin, and Bafilomycin A1. We found that siRNAs are over-accumulated intracellularly and colocalized with a late endosome marker Rab7 in Vacuolin-1 treated cells, suggesting Vacuolin-1 inhibits the cytoplasmic release of lipid siRNA complexes from late endosomes. We propose that Vacuolin-1 could potentially be used to control the effects of lipid nanoparticle-based RNAi and gene therapy drugs." @default.
• W2914686093 created "2019-02-21" @default.
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• W2914686093 date "2019-03-01" @default.
• W2914686093 modified "2023-09-24" @default.
• W2914686093 title "Autophagy inhibitor Vacuolin-1 interferes with lipid-based small interference RNA delivery" @default.
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• W2914686093 doi "https://doi.org/10.1016/j.bbrc.2019.01.121" @default.
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