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PepFect14 (PF14) is a cell-penetrating peptide (CPP) designed as a non-viral delivery vehicle for nucleic acid therapeutics, including mRNA, plasmid DNA (pDNA), small interfering RNA (siRNA), microRNA (miRNA), and splice-correcting oligonucleotides (SCOs). Derived from stearylated transportan 10 (TP10), PepFect14 features the replacement of lysine residues with ornithine, which enhances its resistance to serum proteases and improves transfection efficiency. It forms stable nanoparticles with nucleic acids through electrostatic interactions. Research led by the University of Tartu, Stockholm University, and Radboud University Medical Center has demonstrated its utility in delivering therapeutic cargos in vitro and in vivo. Specifically, PF14-mRNA nanoparticles enter cells via endocytic pathways (such as macropinocytosis and clathrin-mediated endocytosis) and have shown potential for treating inflammatory skin conditions, such as irritant contact dermatitis, and ovarian cancer, without provoking harmful immune responses.
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