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SCI 13 October 2024 Transferrin receptor targeting chimeras for membrane protein degradation (Nature; IF:50.5) Zhang D, Duque-Jimenez J, Facchinetti F, Brixi G, Rhee K, Feng WW, Jänne PA, Zhou X: Transferrin receptor targeting chimeras for membrane protein degradation. Nature 2024. Correspondence to: xin_zhou1@dfci.harvard.edu Abstract Cancer cells require high levels of iron for rapid proliferation, leading to significant upregulation of cell-surface transferrin receptor 1 (TfR1), which mediates iron uptake by binding to the iron-carrying protein transferrin. Leveraging this phenomenon and the fast endocytosis rate of TfR1, we developed transferrin receptor targeting chimeras (TransTACs), a heterobispecific antibody modality for membrane protein degradation. TransTACs are engineered to drive rapid co-internalization of a target protein of interest and TfR1 from the cell surface, and to enable target protein entry into the lysosomal degradation pathway. We show that TransTACs can e
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