Tunable gene control via RNA splicing with a clinically approved small molecule - PubMed
3 hours ago
- #Gene therapy
- #Risdiplam
- #RNA splicing
- RisdiON is a compact inducible gene control system that uses risdiplam, a clinically approved oral drug, to regulate transgene expression via RNA splicing.
- The system leverages risdiplam-responsive sequences and the endogenous splicing machinery, eliminating the need for immunogenic exogenous proteins.
- RisdiON features a split-ATG architecture to express native, tag-free proteins, offering robust, dose-dependent induction with minimal leakiness.
- It has been successfully tested in various contexts, including immortalized cell lines, hiPSCs, primary T cells (for inducible CAR expression), and Cas9 gene editing.
- Reversible transgene expression in vivo was achieved through adeno-associated virus (AAV) delivery, demonstrating modularity and functionality across diverse promoters.
- Supported by F. Hoffmann-La Roche Ltd and Genentech Inc., RisdiON presents a safe, titratable, and reversible tool for advancing gene and cell therapies.