人工ＲＮＡを活用した高効率・汎用的な細胞リプログラミング技術の確立

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In this project, we first demonstrated that by a simple methylation of pseudouridine can significantly alter the thermodynamic properties of RNAs, which results in the enhancement of mRNA expression rate, and ambiguously influence the binding between microRNAs with their complementary RNA sequences.We have then use T7 polymerase based in vitro RNA synthesis to produce mRNAs containing various types of methylated nucleotide, and examined their performance in a variety of cells, including iPSC and differentiated iPSCs. We found that on all cell types tested, including iPSCs, the mRNAs containing methylated pseudouridine exhibited significantly higher protein production rate, indicating the impact of methylation of RNA is conserved among cell types. However, the fold difference in protein expression between native and methylated mRNAs are different for each cell types, suggesting each cell response to RNA methylation in different ways.