Introducing "superGR," a novel synthetic glucocorticoid receptor fusion protein designed to enhance glucocorticoid therapy by providing ligand-independent activation and improved gene regulation for inflammatory diseases.
Background: Glucocorticoids are widely used to treat inflammatory conditions like severe alcoholic hepatitis and sepsis, but their effectiveness is often hindered by significant side effects and the development of resistance, particularly in the liver. Existing therapies rely on ligands that can cause undesired, broad activation of the glucocorticoid receptor, which restricts their clinical utility. These challenges necessitate the development of more selective and effective therapeutic approaches that can activate protective genes while minimizing harmful inflammatory responses and adverse effects.
Technology Overview: The technology centers on the creation of "superGR," a novel fusion protein that functions as a constitutively active glucocorticoid receptor independent of ligand binding. This means it can continuously activate the receptor without needing traditional glucocorticoid molecules, which helps to avoid the use of "dirty" ligands that cause off-target effects. "SuperGR" is engineered through precise mutations that enhance its ability to selectively turn on protective genes and suppress pro-inflammatory genes more efficiently than current treatments like Dexamethasone. By addressing the core challenges of glucocorticoid resistance in the liver and unwanted side effects from conventional receptor activation, this synthetic receptor provides a more targeted and effective approach to therapy. The technology also contemplates advanced delivery mechanisms, including gene therapy vectors such as lipid nanoparticles and adeno-associated viruses, to enable efficient and focused delivery of the "superGR" gene to affected tissues. This method enhances treatment precision and reduces systemic exposure, offering significant therapeutic advantages.
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Advantages: • Ligand-independent activation reduces reliance on external drugs, minimizing complications related to "dirty" ligands. • Improved gene regulation enhances treatment efficacy by promoting protective effects and suppressing inflammation more effectively. • Reduced side effects compared to conventional glucocorticoid therapies due to targeted receptor modifications. • Potential for gene therapy-based delivery enables precise targeting and sustained therapeutic benefit.
Applications: • Treatment of severe alcoholic hepatitis and other inflammatory liver diseases. • Management of sepsis through enhanced modulation of immune responses. • Possible extension to other inflammatory and immune-related conditions requiring glucocorticoid therapy. • Use in advanced gene therapy platforms for targeted and controlled glucocorticoid receptor activation.
Intellectual Property Summary: Patent application 63/928,373 filed on 12/1/2025
Stage of Development: TRL 3
Licensing Status: This technology is available for licensing.