Müller Thomas, Gieß Sophie, Maier Fanny, Hofacker Lara, Stenger Luca, Parker Larissa, Grosse Robert, Schmidt Gudula
Institute for Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany.
Toxins (Basel). 2025 Sep 5;17(9):448. doi: 10.3390/toxins17090448.
produces a syringe-like toxin complex to inject toxic enzymes into cells. We demonstrated that the recombinant toxin complex (PTC) can be engineered for translocation of foreign cargo proteins across cellular membranes. We showed that the system is suitable for injection of trimeric affibodies into mammalian cells in order to influence crucial signaling pathways. As proof of principle, we inhibited Ras-driven tumor cell proliferation by injection of an affibody which interacts with the Ras binding domain of Raf kinase. The system described here could be applicable to target a wide range of signaling molecules for cell biological or therapeutic intervention.
产生一种类似注射器的毒素复合物,用于将有毒酶注入细胞。我们证明了重组毒素复合物(PTC)可经改造用于将外源货物蛋白转运穿过细胞膜。我们表明该系统适用于将三聚体亲和体注入哺乳动物细胞,以影响关键信号通路。作为原理验证,我们通过注入一种与Raf激酶的Ras结合域相互作用的亲和体,抑制了Ras驱动的肿瘤细胞增殖。此处描述的系统可应用于靶向多种信号分子,以进行细胞生物学或治疗干预。