Development of functional polycation for efficient mRNA delivery system

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Polyion complexes formed from nucleic acids and polycations, which were termed polypex, has been attracted attention because of their therapeutic potential. Messenger RNA (mRNA) was recognized as a new candidate for the safe nucleic acids drug because of no risk of mutagenesis. However mRNA possessed labile nature in physiological condition. Herein, we synthesized the polycations possessing slightly different chemical structure in their side chain and compared their mRNA delivery mechanism to get the insight for the design of polycations achieving safe and efficient mRNA delivery. In the results, the polycations possessing odd-numbered aminoethylene units in their side chain showed efficient mRNA delivery and higher cytoplasmic stability than those even one. We concluded that the fine-tuning of chemical structure of polycations can enhance the cytoplasmic stability and mRNA expression of polyplexes.