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NRF2 activation strategies compared in this study: (A) Small molecules targeting KEAP1 inhibit NRF2-KEAP1 interaction. (B) Alternatively, hNRF2 cmRNA transfection results in endosomal uptake of the cmRNA-lipid nanoparticle. Following endosomal escape, the hNRF2 cmRNA is translated into NRF2 protein. Both pathways culminate with NRF2 translocation into the nucleus and upregulation of antioxidant gene expression.
