Ecdysone receptor-based RheoSwitch Therapeutic System (RTS) (RTS)

The Ecdysone receptor (EcR)-based RheoSwitch Therapeutic System (RTS) is a synthetic, ligand-inducible gene regulation platform used to provide precise control over the timing and level of therapeutic protein production. It consists of a chimeric transcription factor derived from the insect ecdysone receptor and a retinoid X receptor (RXR) partner, which remains inactive in the absence of a specific ligand. In the context of FCX-013, autologous fibroblasts are genetically modified to express Matrix Metalloproteinase 1 (MMP-1) under the control of this switch. When the small-molecule activator veledimex is administered, it binds to the RTS complex, triggering the localized expression of MMP-1 to degrade excess collagen in patients with localized scleroderma. This system is highly specific because the ecdysone receptor is not naturally present in mammalian cells, minimizing off-target effects and interference with endogenous human signaling pathways.

Other names

RheoSwitchEcR-based gene switchEcdysone receptor gene expression systemVeledimex-activated gene switchRTS-MMP1

Veledimex acts as a small-molecule ligand that binds to the chimeric ecdysone receptor (EcR) component of the RheoSwitch Therapeutic System. Upon binding, the receptor complex undergoes a conformational change that allows it to bind to specific DNA response elements in the promoter region of the target transgene (e.g., MMP-1), thereby initiating transcription and subsequent protein synthesis in a dose-dependent manner.