Recently, Dr. Jian Liu’s group from Zhejiang University-University of Edinburgh Institute (ZJE) and the collaborators, Pro. Shiqun Shao from College of Chemical and Biological Engineering
of Zhejiang University, published an article entitled “A plug-and-play monofunctional platform for targeted degradation of extracellular proteins and vesicles” in Nature Communications. https://doi.org/10.1038/s41467-024-51720-z
Existing strategies use bifunctional chimaeras to mediate extracellular protein degradation. However, these strategies rely on specific lysosome-trafficking receptors to facilitate lysosomal delivery, which may raise resistance concerns due to intrinsic cell-to-cell variation in receptor expression and mutations or downregulation of the receptors. Another challenge is establishing a universal platform applicable in multiple scenarios. Here, the research team develops MONOTAB (MOdified NanOparticle with TArgeting Binders), a plug-and-play monofunctional degradation platform that can drag extracellular targets into lysosomes for degradation. MONOTAB harnesses the inherent lysosome-targeting ability of certain nanoparticles to obviate specific receptor dependency and the hook effect. To achieve high modularity and programmable target specificity, the streptavidin-biotin interaction is utilized to immobilize antibodies or other targeting molecules on nanoparticles, through an antibody mounting approach or by direct binding. This study reveals that MONOTAB can induce efficient degradation of diverse therapeutic targets, including membrane proteins, secreted proteins, and even extracellular vesicles.
Targeted degradation of extracellular proteins or vesicles mediated by MONOTABs
Pro. Shiqun Shao and Pro. Jian Liu are the corresponding authors. In addition, the PhD student Qian Tang (ZJE, 2021 entry) participated in this research as the co-first author.
About Jian Liu’s lab
Jian Liu's group is now interested in investigating lung squamous cell carcinoma development and treatment using genetic mouse models and AI+ multi-omics, especially the research direction on cancer immunology and 3D genome. He has published over 50 papers, including publications in the past three years, as a co-corresponding author in Nature Communications (2), Advanced Science, Oncogene, Molecular Oncology journals. Moreover, his lab developed a multi-omics web database Omics3D (http://omics3d.net/) to investigate the de novo functional genome during cancer development.
Email:JianL@intl.zju.edu.cn
Jian Liu’s lab (https://person.zju.edu.cn/liujian) is recruiting postdoc and Ph.D. students, including the single degree from University of Edinburgh.
