Stearylated antimicrobial peptide [D]-K6L9 with cell penetrating property for efficient gene transfer

•Stearyl-[D]-K6L9 is a novel type of antimicrobial peptide-based gene vector.•Stearyl-[D]-K6L9 delivers plasmids into cells by endocytosis.•Stearyl-[D]-K6L9 displays high endosome-lytic activity.•Stearyl-[D]-K6L9 displays high transfection efficiency. Stearyl-cell penetrating peptides (CPPs) have been proved to be efficient nonviral gene vectors. Due to the similarities between antimicrobial peptides and CPPs, we constructed a novel type of gene vectors by introducing stearyl moiety to the N-terminus of antimicrobial peptide [D]-K6L9. In this study, stearyl-[D]-K6L9 delivered plasmids into cells by clathrin- and caveolin-mediated endocytosis. Gratifyingly, stearyl-[D]-K6L9 exhibited high transfection efficiency and almost reached the level of Lipofectamine 2000. Taken together, the combination of the stearyl moiety with [D]-K6L9 provides a novel framework for the development of excellent nonviral gene vectors.