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shRNA targeting NDUFA7 + shRNA targeting NDUFS4 is a combination RNA interference therapy consisting of two short hairpin RNAs (shRNAs) designed to simultaneously knock down the expression of NDUFA7 and NDUFS4, both accessory subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase). NDUFA7 and NDUFS4 are essential nuclear-encoded components of the electron transport chain involved in electron transfer from NADH to ubiquinone, and their knockdown disrupts complex I biogenesis and function, leading to impaired oxidative phosphorylation, increased reactive oxygen species (ROS), and mitochondrial dysfunction. This approach has been used experimentally to study mitochondrial homeostasis, such as in mesenchymal stem cell senescence models where downregulation of these subunits contributes to OXPHOS defects, particularly affecting complex I assembly.
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