Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

Plasmid DNA based gene delivery has been widely utilized among both pre-clinical and clinical gene therapy studies. However, therapeutic efficiency is usually limited by the size and potential immune-stimulation issue of plasmid backbone. As an alternative form of genetic material, chemically modified messenger RNA (mRNA) provides a promising alternative to plasmid DNA. In this work, an in vitro transcription mRNA encoding vesicular stomatitis virus matrix protein (VSVMP) was delivered by a cationic liposome–protamine complex, resulting in high mRNA transporting and expression efficiency. The liposome–protamine complex delivered VSVMP mRNA strongly inhibits the growth of C26 tumor cells through inducing apoptosis, while obvious tumor regressions were achieved on both abdominal cavity metastatic and subcutaneous xenograft models in vivo with high safety. Our results also demonstrated that the liposome–protamine–mRNA complex was as potent as its plasmid DNA counterpart, showing strong potential in further colon cancer therapy.