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Gene therapies can be safe and beneficial when administered in controlled clinical settings and for well-defined conditions

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KochMDeKoskySTGoodmanMSunJFurtadoJDFitzpatrickALet al

Mechanistically, autoantibodies and interferon- present in the serum induce neutrophil ferroptosis through enhanced binding of the transcriptional repressor CREM to the glutathione peroxidase 4 ( Gpx4 , the key ferroptosis regulator) promoter, which leads to suppressed expression of Gpx4 and subsequent elevation of lipid-reactive oxygen species

GPX4 requirements in vivo are not consistent across macrophage subsets and are limited to alternatively activated macrophages whose proliferation or expansion is reduced after GPX4 deletion [78]

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