Transferrin receptor targeting chimeras for membrane protein degradation.

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^1-3. Leveraging this phenomenon and the fast endocytosis rate of TfR1 (refs. ^4,5), 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 efficiently degrade a diverse range of single-pass, multi-pass, native or synthetic membrane proteins, inc

SUBMITTER: Zhang D 

PROVIDER: S-EPMC11839386 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature