GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320370/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320370GEOGSEfalseTunable Gene Control via RNA Splicing with clinically approved small moleculePrecise transgene regulation is crucial for safe and effective gene and cell therapies. Current inducible systems often rely on immunogenic exogenous proteins or non-clinically approved inducers, hindering clinical translation. We developed RisdiON, a compact inducible system controlled by risdiplam, a clinically approved oral drug that acts via splicing modulation. RisdiON utilizes risdiplam-responsive sequences for precise transgene control via endogenous splicing machinery, bypassing exogenous protein regulators, while its 'split-ATG' architecture ensures the expression of native, tag-free proteins. This approach provides robust, dose-dependent induction with minimal leakiness. RisdiON demonstrated broad utility, controlling various transgenes in immortalized cell lines and hiPSCs, enabling inducible CAR expression in primary T cells, and regulating Cas9 for precise gene editing. Additionally, adeno-associated virus (AAV)-delivered RisdiON achieved reversible transgene expression in vivo. The platform is modular and functional across diverse promoters, offering a safe, titratable, and reversible tool when coupled with an orally bioavailable drug to advance next-generation therapies.2026/04/30GSE320370GSM9541925GSM9541926GSM9541927GSM9541928GSM9541908GSM954192224676320370Homo sapiens