Anne von Mässenhausen, Marlena Nastassja Schlecht, Kristina Beer, Francesca Maremonti, Wulf Tonnus, Alexia Belavgeni, Shubhangi Gavali, Karolin Flade, Joel S Riley, Nadia Zamora Gonzalez, Anne Brucker, Jorunn Naila Becker, Mirela Tmava, Claudia Meyer, Mirko Peitzsch, Christian Hugo, Florian Gembardt, Jose Pedro Friedmann Angeli, Stefan R Bornstein, Stephen W G Tait, Andreas Linkermann
Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. Genetically targeting mitochondrial antiviral-signaling protein (MAVS) reversed the siRNA-mediated sensitizing effect, but no activation of canonical MAVS signaling, which involves phosphorylation of IkBα and interferon regulatory transcription factor 3 (IRF3), was observed...
March 15, 2024: Science Advances