2025-07-01 京都大学iPS細胞研究所
図1. プロテインスプライシングを活用したスプリットRNAスイッチ
<関連情報>
- https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/250701-180000.html
- https://www.nature.com/articles/s41467-025-60392-2
スプリットRNAスイッチは、細胞種特異的な遺伝子発現を可能にする翻訳前および翻訳後の制御をオーケストレーションする Split RNA switch orchestrates pre- and post-translational control to enable cell type-specific gene expression
Itsuki Abe,Hirohisa Ohno,Megumi Mochizuki,Karin Hayashi & Hirohide Saito
Nature Communications Published:01 July 2025
DOI:https://doi.org/10.1038/s41467-025-60392-2
Abstract
RNA switch is a synthetic RNA-based technology that controls gene expression in response to cellular RNAs and proteins, thus enabling cell type-specific gene regulation and holding promise for gene therapy, regenerative medicine, and cell therapy. However, individual RNA switches often lack the specificity required for practical applications due to low ON/OFF ratios and difficulty in finding distinct and single biomolecule targets. To address these issues, we present “split RNA switches” that integrate outputs from multiple RNA switches by exploiting protein splicing. We show that split RNA switches significantly improve the ON/OFF ratio of microRNA-responsive ON switch system by canceling leaky OFF level in human cells. Using this approach, we achieve efficient cell purification using drug-resistance genes based on endogenous microRNA profiles and CRISPR-mediated genome editing with minimal off-target-cell effects. Additionally, we demonstrate RNA-based synthetic circuits using split RNA switches to enable the detection of multiple microRNAs and proteins with logical operations. Split RNA switches highlight the potential of post-translational processing as a versatile and comprehensive strategy for advancing mRNA-based therapeutic technologies.
