ArticleNucleic acids research2025
A mediator-free sonogenetic switch for therapeutic protein expression in mammalian cells.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Truncated Gpr114-based ultrasound-hypersensitive gene circuit for controlled expression of therapeutics.Nature communications · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Modular Scalable Synthetic Gene Circuits for Complex Functions Within Minimal Computational Layers in Human Cells.Nature communications · 2026Article
- Inducible CRISPR/Cas systems in precision oncology: Current applications and future perspectives.Clinical and translational medicine · 2026Review
- Engineered romidepsin biosynthetic pathways in Escherichia coli Nissle 1917 improve the efficacy of bacteria-mediated cancer therapy.PLoS biology · 2026Article
- Traceless Regulation of Genetic Circuitry.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- On-demand cancer immunotherapy via single-cell encapsulation of synthetic circuit-engineered cells.Science advances · 2026Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
An ultrasound-responsive transgene circuit can provide non-invasive, spatiotemporally precise remote control of gene expression and cellular behavior in synthetic biology applications. However, current ultrasound-based systems often rely on nanoparticles or harness ultrasound's thermal effects, posing risks of tissue damage and cellular stress that limit their therapeutic potential. Here, we present Spatiotemporal Ultrasound-induced Protein Expression Regulator (SUPER), a novel gene switch enabling mediator-free, non-invasive and direct regulation of protein expression via ultrasound in mammalian cells. SUPER leverages the mammalian reactive oxygen species (ROS) sensing system, featuring KEAP1 (Kelch-like ECH-associated protein 1), NRF2 (nuclear factor erythroid 2-related factor 2), and antioxidant response element (ARE) as its core components. We demonstrate that low-intensity (1.5 W/cm2, ∼45 kHz), brief (40 s) ultrasound exposure generates non-toxic levels of ROS, activating the KEAP1/NRF2 pathway in engineered cells and leading to the controlled expression of target gene(s) via a synthetic ARE promoter. The system exhibits robust expression dynamics, excellent reversibility, and functionality in various cell types, including human mesenchymal stem cell-derived lines (hMSC-TERT). In a proof-of-concept study, ultrasound stimulation of subcutaneously implanted microencapsulated engineered cells stably expressing the sonogenetic circuit in a type 1 diabetic mouse model triggered sufficient insulin production to restore normoglycemia. Our work highlights ultrasound's potential as a precise and non-invasive tool for advancing cell and gene therapies in personalized medicine.
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Registered trials
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