Related Experiment Video
Updated: Jan 14, 2026
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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
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Extracellular vesicle-based targeted protein degradation platform for multiple extracellular proteins
Bide Tong1,2, Xiaoguang Zhang1, Dingchao Zhu1
1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
EMBO Molecular Medicine
|January 12, 2026
Summary
Extracellular vesicles (EVs) are degraded via autophagy, a process harnessed to create an EV-based targeted protein degradation (EVTPD) platform. This novel platform effectively degrades extracellular proteins and reduces inflammation.
Area of Science:
- Biotechnology
- Cell Biology
- Drug Discovery
Background:
- Targeted protein degradation (TPD) offers a therapeutic strategy for undruggable targets.
- Extracellular vesicles (EVs) show promise as TPD platforms, but their degradation mechanism is unclear.
Purpose of the Study:
- To elucidate the degradation pathway of EVs.
- To develop a modular EV-based targeted protein degradation (EVTPD) platform.
Main Methods:
- Investigated EV degradation using autophagy-mediated lysosomal pathways.
- Identified MAP1LC3B recognition of SQSTM1 LIR motifs in EV degradation.
- Engineered EVs with LIR motifs and target-binding domains for EVTPD construction.
Main Results:
- Autophagy-mediated lysosomal degradation is the primary route for EVs.
- The developed EVTPD selectively degraded extracellular proteins without cell receptors.
- Dual-targeting EVTPD demonstrated potent anti-inflammatory effects in preclinical models.
Conclusions:
- Established a modular EV-based TPD strategy utilizing autophagy.
- Demonstrated the potential of EVTPD for multi-targeting extracellular proteins and treating inflammatory diseases.
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