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repRNA-IL12 is a self-replicating messenger RNA (repRNA) therapy designed to express Interleukin-12 (IL-12), a potent proinflammatory cytokine that coordinates innate and adaptive immune responses. The construct typically utilizes a viral replicon platform, such as one derived from the Venezuelan Equine Encephalitis (VEE) virus, which allows the RNA to self-amplify within target cells. This mechanism results in significantly higher and more sustained levels of IL-12 protein production compared to conventional modified mRNA (modRNA). repRNA-IL12 is formulated in lipid nanoparticles (LNPs), often using specialized cationic lipids like TT3, to facilitate efficient intracellular delivery and induce immunogenic cell death (ICD). The expressed IL-12 binds to IL-12 receptors on natural killer (NK) cells and T cells, stimulating the production of interferon-gamma (IFN-γ) and enhancing the cytolytic activity of the immune system against tumors. It is primarily being investigated for the treatment of various solid tumors, including melanoma and breast cancer, via intratumoral or systemic administration.
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