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GPX4 small interfering RNA
- Development stage
- Preclinical
- Lead developer
- Mayo Clinic
- Modality
- RNA Aptamers → RNA Therapeutics → Nucleic Acid Therapeutics, Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Nanoparticles → Drug Delivery Systems, DNA Aptamers → DNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Intravenous
01
Overview
GPX4 small interfering RNA is an experimental RNA interference (RNAi) therapeutic designed to silence the expression of Glutathione Peroxidase 4 (GPX4). GPX4 is a critical antioxidant enzyme that protects cells from ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. In the context of BAP1-mutant cholangiocarcinoma (CCA), which exhibits resistance to ferroptosis due to metabolic rewiring, targeting GPX4 aims to overcome this resistance and induce tumor cell death. The therapeutic is delivered using engineered EpCAM-aptamer-coated lactosomes, which selectively target EpCAM-expressing cancer cells to minimize systemic toxicity. Pre-clinical studies in syngeneic liver orthotopic CCA murine models have demonstrated that this approach can robustly suppress tumor growth.
- Other names
- GPX4 siRNAGPX-4 siRNAGPX 4 siRNAEpCAM-aptamer-coated lactosomes carrying GPX4 siRNA
02
Targets
GPX4 (Glutathione peroxidase 4)
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