Sortilin-Mediated Rapid, Precise and Sustained Degradation of Membrane Proteins via mRNA-Encoded Lysosome-Targeting Chimera.

ABSTRACT: Recent advances in lysosome-targeting degradation technologies have introduced strategies to regulate therapeutic membrane proteins (MPs), potentially transforming treatment paradigms. However, challenges persist, including limited degradation precision due to the broad distribution of lysosome-targeting receptors (LTRs), as well as the high cost and complexity of recombinant protein production or chemical synthesis. Herein, it identifies sortilin as a promising LTR, highly expressed in malignancies but minimally present in healthy tissues outside the nervous system. Using AlphaFold-Multimer, it screened for a specific non-endogenous protein binder to sortilin and developed a modular, mRNA-encoded lysosomal targeting chimera (MedTAC) strategy, enabling rapid design and precise degradation

SUBMITTER: Chang X 

PROVIDER: S-EPMC12224941 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature