Proteomics

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Engineering platelets as targeted protein degraders


ABSTRACT: We covalently tethered the POI ligand to heat shock protein 90 (HSP90) within platelets through ligand-directed covalent labeling method mediated by the N-acyl-N-alkyl sulfonamide (NASA) linker. These proteolytic platelets, termed DePLT, could selectively accumulate at wound-associated disease sites and then potently degrade the POI by repurposing the critical role of molecular chaperones in protein processing.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): 4t1 Cell

SUBMITTER: Yu Chen  

LAB HEAD: Quanyin Hu

PROVIDER: PXD055866 | Pride | 2025-12-08

REPOSITORIES: Pride

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Publications

Engineered platelets as targeted protein degraders and application to breast cancer models.

Chen Yu Y   Pal Samira S   Li Wen W   Liu Fengyuan F   Yuan Sichen S   Hu Quanyin Q  

Nature biotechnology 20241203 11


Clinical application of chimeric molecules for targeted protein degradation has been limited by unfavorable drug-like properties and biosafety concerns arising from nonspecific biodistribution after systemic administration. Here we develop a method to engineer platelets for degradation of either intracellular or extracellular proteins of interest (POIs) in vivo by covalently labeling heat shock protein 90 (HSP90) in platelets with a POI ligand. The degrader platelets (DePLTs) target wound areas  ...[more]

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