2026-01-20 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/cas_media/202601/t20260120_1145911.shtml
- https://www.cell.com/cell/abstract/S0092-8674(25)01420-5
マルチモーダル超分子標的キメラは生体内での時空間的に分解されたタンパク質分解を可能にする Multimodal supramolecular targeting chimeras enable spatiotemporally resolved protein degradation in vivo
Ji Liu ∙ Tianyu Ma ∙ Rui Yao ∙ Lijuan Li ∙ Qizhen Zheng ∙ Ming Wang
Cell Published:January 16, 2026
DOI:https://doi.org/10.1016/j.cell.2025.12.007
Graphical abstract
Highlights
- SupTAC provides a modular and programmable platform for targeted protein degradation
- SupTAC enables spatiotemporally resolved protein degradation in vivo
- SupTAC demonstrates tissue-specific protein degradation in non-human primates
- Lung-specific degradation of ACSL4 effectively suppresses lung ferroptosis
Summary
Targeted protein degradation (TPD) has transformed strategies for modulating protein function in both basic biology and therapeutic development. However, current strategies often lack the spatial and temporal precision required for in vivo applications. Herein, we report supramolecular targeting chimeras (SupTACs), a modular and programmable platform that enables tissue-specific and temporally controlled protein degradation in vivo. SupTACs self-assemble into supramolecular nanoparticles (SNPs) that co-localize target-binding ligands and E3 ligase recruiters, thereby facilitating proteasomal degradation through multivalent supramolecular proximity. This strategy achieves robust and tissue-specific degradation, including liver and lung specificity, in multiple species up to non-human primates. As a proof of concept, lung-specific degradation of acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) using SupTACs effectively mitigates ferroptosis and pulmonary inflammation in a murine model of acute lung injury. By integrating modularity, tissue specificity, and temporal regulation, SupTACs establish a versatile platform for precise control of protein degradation for interrogating dynamic signaling networks and developing targeted therapeutics.
