Rgenta’s RSwitch Platform Reported to Regulate Gene Therapy Transgene Expression

WOBURN, Mass. – May 13, 2025 – Rgenta Therapeutics, a clinical-stage biotechnology company developing oral small molecules targeting RNA and RNA regulation, announced the presentation of preclinical data demonstrating the potential of its proprietary RSwitch technology to enable fine-tuned control of transgene levels in gene therapy applications. This control is achieved using orally administered small molecules (RDrugs) specifically designed for each indication, offering a range of pharmacokinetic properties. The data was presented at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting in New Orleans, LA.

Dr. Travis Wager, co-founder and chief scientific officer of Rgenta, highlighted that the RSwitch technology is designed to deliver precise temporal control of therapeutic transgene expression over a wide dynamic range, applicable to various gene and cell therapy applications. He explained that unlike existing methods that rely on engineered transcription factors and repurposed pharmacology, Rgenta’s platform creates gene therapy vectors with selective, dose-dependent regulation by orally bioavailable RDrugs. Utilizing massively parallel sequence library screening and deep learning-driven design, Rgenta has developed RDrugs to directly control specific pre-mRNA splicing events necessary for the regulated production of the therapeutic payload via RSwitch.

In a poster presentation on RSwitch for Friedreich’s Ataxia (FA), Rgenta scientists demonstrated up to 4000-fold dose-dependent induction of gene expression by a specific RDrug using RSwitches in both high and low strength promoters. They also presented data from an RSwitch-regulated AAV gene therapy expressing frataxin (FXN) for potential FA treatment. Given the cardiotoxic effects of unregulated FXN overexpression observed in preclinical studies, a regulatable system like RSwitch is highly desirable. The data showed that this RSwitch-regulated FA gene therapy achieved dose-dependent FXN expression in the heart with RDrug, reaching human endogenous FXN levels in mice at low RDrug concentrations. A separate system demonstrated the ability of Rgenta’s RSwitch and a corresponding brain-penetrant RDrug to regulate transgene expression in the brain.

Dr. Simon Xi, co-founder and chief executive officer of Rgenta, emphasized the potential of RSwitch as a game-changing tool for developing safer regulatable gene and cell therapies, showcasing the power of Rgenta’s RNA-targeted small molecule platform. He also highlighted Rgenta’s internal pipeline focused on inhibiting disease-driving targets in oncology and neurological disorders and expressed interest in partnering with gene and cell therapy companies to enhance the clinical success of gene replacement therapies for diseases like FA.

About RSwitch: RSwitch is Rgenta’s proprietary regulatable gene therapy system that allows for oral, small molecule drug control of transgene levels in gene and cell therapy applications. It functions as a “dimmer” switch, making transgene expression dependent on the administration of an oral RDrug. The level of gene expression is directly proportional to the drug dosage, enabling precise control of therapeutic protein production. Rgenta has demonstrated the feasibility of RSwitch in vitro and in vivo, achieving dose-dependent expression of reporter transgenes following small molecule administration and is actively seeking strategic partnerships to leverage its versatile control across various gene and cell therapy applications.