Promising improvements in synthesis of stable and nonimmunogenic messenger RNA (mRNA) have enhanced the potential for mRNA in in situ production of therapeutic proteins. In this study, we explored the delivery of an mRNA expressing the tumor necrosis factor-related apoptosis-inducing ligand protein (mTRAIL) into breast cancer cells and human bone marrow stromal cells (hBMSCs) by using aliphatic lipid-modified small molecular weight polyethylenimine (PEI) carriers. The duration and extent of TRAIL secretion after mRNA delivery were dependent on the cell type, but mRNA delivery consistently showed earlier and higher protein expression compared with plasmid DNA delivery. Higher TRAIL-induced cytotoxicity and apoptosis induction were evident in breast cancer cells after mTRAIL transfection. In addition, hBMSCs transfected with mTRAIL were able to effectively kill breast cancer cells after coculture. mTRAIL delivery with the lipopolymers resulted in significant inhibition of breast cancer tumor growth in a xenograft model in mice. We conclude that an mRNA-based approach to TRAIL expression is a highly promising approach to retard the growth of breast cancer cells.
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