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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): Blood Platelet

SUBMITTER: Yu Chen

LAB HEAD: Quanyin Hu

PROVIDER: PXD055828 | Pride | 2025-12-08

REPOSITORIES: Pride

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			Action	DRS
	20231025_IP_C_1.raw	Raw
	20231025_IP_C_2.xlsx	Xlsx
	20231025_IP_C_2_4ul.raw	Raw
	20231025_IP_T_1.raw	Raw
	20231025_IP_T_2.xlsx	Xlsx

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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]

PMID: 39627511

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Engineering platelets as targeted protein degraders

Project description: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.

2025-12-08 | PXD055866 | Pride

U1 RAP-RNA-Seq analysis of A2Lox mouse embryonic stem cells treated with a control or Srrt-specific siRNA

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RNA-immunoprecipitation of mTRAN1-GFP

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CutnRun directed against O-GlcNac in the human DLD-1 cell line with doxycycline treatment to induce RNA Polymerase II degradation

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Project description:To explore the diverse platelet microRNA (miRNA) expression between high platelet reactivity (HPR) and low platelet reactivity (LPR) patients with acute coronary syndromes (ACS), we enrolled a cohort of ACS patients and performed miRNA expression profiling of platelets from four HPR and four LPR patients using human miRNA microarray system. VerifyNow P2Y12 assay was applied to indentify HPR and LPR. Venous blood was drawn from the patients and was centrifuged to prepare platelets. Among the candidate differentially expressed miRNAs, miR-15b expression was further confirmed to be lower in platelets of 22 HPR patients than 17 LPR by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). We enrolled a consecutive cohort of 290 ACS patients and assessed the platelet reactivity using VerifyNow P2Y12 assay. In this study, HPR was defined as M-bM-^IM-%300 platelet reactivity unit (PRU) while LPR <170 PRU. miRNA microarray analysis was performed in platelets of four HPR and four LPR patients with ACS.

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Calibrating ChIP-seq with nucleosomal internal standards to measure histone modification density genome-wide

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