2025-07-07 京都大学 iPS細胞研究所
図1. ハイブリッドスイッチの概略図
<関連情報>
- https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/250707-100000.html
- https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(25)00163-5
精密なタンパク質発現制御のためのマイクロRNA応答性ON-OFFハイブリッドmRNAスイッチ MicroRNA-responsive ON-OFF hybrid mRNA switch for precise protein expression control
Kaito Masaki ∙ Yoshihiko Fujita ∙ Hirohide Saito
Molecular Therapy Nucleic Acids Published:June 16, 2025
DOI:https://doi.org/10.1016/j.omtn.2025.102609
Abstract
Messenger RNA (mRNA) technology is gaining attention for its potential in developing next-generation therapeutics. However, developing effective protein expression control technologies to regulate mRNA translation, particularly in a cell type- and tissue-specific manner, remains challenging. To achieve enhanced precision in translational regulation, we developed a microRNA (miRNA)-sensing hybrid mRNA switch, integrating an ON-type switch, which activates translation by detecting specific miRNAs expressed in target cells, into an OFF-type switch, which represses translation by sensing another miRNA in non-target cells. We first investigated effective module sequences after the poly(A)-tail for the ON-type mRNA switch to ensure appropriate translational activation in response to target cell-specific miRNAs. Moreover, the hybrid mRNA switch with a dual miRNA-sensing system reduced expression leakage in non-target cells and enhanced ON/OFF selectivity in vitro human cell cultures and in vivo mouse model. This ON-OFF hybrid mRNA switch technology allows for the selective expression of target proteins in designated cells and holds promise for the next generation of mRNA therapeutics.
