ArticleNature communications2025
Split RNA switch orchestrates pre- and post-translational control to enable cell type-specific gene expression.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- miRBind2 enables sequence-only prediction of miRNA binding and transcript repression.Bioinformatics (Oxford, England) · 2026Article
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Messenger RNA-encoded reporters for monitoring cellular stress and bioenergetics.Scientific reports · 2026Article
- Enhancing small-molecule-mediated translational control through multivalent RNA aptamers.Nucleic acids research · 2026Article
- "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Unraveling the influence of TGF-β rs9282871 and miRNA let-7c relative expression on TGF-β production in hepatocellular carcinoma patients.Journal, genetic engineering & biotechnology · 2026Article
- Nanotechnology-Assisted Co-Delivery of Immunotherapeutic Agents for Targeting Ovarian Cancer: Prospects and Challenges.International journal of nanomedicine · 2026Review
- Heparin-Conjugated Silver Nanoparticles via Amide Chemistry for Selective Targeting of Triple-Negative Breast Cancer and Pathogenic Fungi.International journal of nanomedicine · 2026Article
Corrections and comments
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Authors and funding
5 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.