A research study by Itsuki Abe (D1 student) has been published in Nature Communications

2025/07/18

A research project led by Itsuki Abe, a doctoral student (Special Research Student), Hirohisa Ohno, Assistant Professor (CiRA), Megumi Mochizuki, Technical Staff (CiRA), and Karin Hayashi, Technical Staff (CiRA), was published online in the international scientific journal Nature Communications on July 1, 2025 (UK time).

 

Professor Hirohide Saito and Special Research student Itsuki Abe team has developed the split RNA switch, an RNA-based system that significantly enhances precise gene expression in targeted cells. This innovation addresses the limitations of traditional RNA switches, which often suffer from "leaky" translation.
The split RNA switch uses protein splicing to ensure functional protein formation only when specific fragments are correctly combined. This method dramatically suppresses unintended protein expression, improving the signal-to-noise ratio dramatically.
This technology has proven versatile, enabling cell-type specific control in various applications, including fluorescent reporters, antibiotic resistance for cell selection, and inducing cell death. It has also been successfully applied to CRISPR-Cas9 genome editing, achieving highly specific gene editing in human cells, including iPS cells, and minimizing off-target edits in disease models like Duchenne muscular dystrophy.
The researchers further developed multi-input logic gates using this system, allowing complex intracellular decision-making based on combinations of miRNAs and proteins. They demonstrated the first RNA-only three-input AND gate.
This study is the first to combine mRNA-based translational regulation with post-translational protein splicing. The split RNA switch offers a modular, scalable, and RNA-only platform for precise gene control, holding immense potential for gene therapy, regenerative medicine, and synthetic biology, paving the way for advanced, "intelligent" RNA therapeutics.

 

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Papers
Journal: Nature Communications

Title: Split RNA switch orchestrates pre- and post-translational control to enable cell type-specific gene expression
Authors: Itsuki Abe1,2,3,4, Hirohisa Ohno1*, Megumi Mochizuki1, Karin Hayashi1, Hirohide Saito1,3* (*:Corresponding author)
Affiliations:
1Center for iPS Cell Research and Application, Kyoto University
2Graduate School of Medicine, Kyoto University
3Institute for Quantitative Biosciences, The University of Tokyo
4Department of Bioengineering, School of Engineering, The University of Tokyo

URL: https://www.nature.com/articles/s41467-025-60392-2