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- W4380148845 abstract "Cellular uptake of exogenous nucleic acids is inhibited in pathological tissues accompanied by excessive expression of matrix metalloproteinases (MMPs). We show that CO, as a regulator of membrane function, can reactivate uptake of agomir (Ago) in pathological condition via RAB5-mediated endocytic pathway. Herein, a responsive nanoparticle-crosslinked injectable hydrogel (CO-Ago gel) was engineered as a prototype for co-delivering CO and Ago to inhibit MMP overexpression in accordance with the disease severity. Compared to a typical matrix-enhanced gene therapy (Ago gel), CO-Ago gel significantly promoted Ago uptake, achieving an order of magnitude improvement of targeted gene expression under pathological conditions (11.2-fold for cardiomyocyte and 15.3-fold for primary fibroblasts). The therapeutic effect of CO-Ago gel on MMP overexpression was assessed in rat models of myocardial ischemia reperfusion and diabetic skin wound healing. The results suggest CO-enhanced transfection could contribute to the development of next-generation adjuvants for gene-based therapies and vaccines in vivo." @default.
- W4380148845 created "2023-06-11" @default.
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- W4380148845 date "2023-08-01" @default.
- W4380148845 modified "2023-10-15" @default.
- W4380148845 title "CO enhances agomir transfection under pathological conditions to inhibit MMP overexpression" @default.
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- W4380148845 doi "https://doi.org/10.1016/j.nantod.2023.101898" @default.
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