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Updated: Sep 20, 2025
Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line
Published on: April 13, 2022
Machine-learning-assisted universal protein activation in living mice.
Xin Wang1, Yuan Liu2, Zhenchao Wang3
1Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China.
Researchers developed CAGE-Proxvivo, a novel strategy for precise control of protein activation and interactions in living mice. This method enables on-demand functional restoration of proteins and targeted therapeutic interventions in vivo.
Area of Science:
- Biochemistry
- Molecular Biology
- Chemical Biology
Background:
- Precise control of protein function in vivo is essential for gain-of-function studies.
- Existing methods often lack the specificity or temporal control needed for complex biological systems.
Purpose of the Study:
- To develop a universal strategy for on-demand protein activation and protein-protein interaction modulation in living animals.
- To establish a platform for time-resolved biological studies and therapeutic interventions.
Main Methods:
- Utilized machine-learning-assisted evolution of aminoacyl-tRNA synthetases (aaRSs) to incorporate chemically caged amino acids.
- Designed "decaging sites" to transiently block protein function.
- Employed small-molecule-triggered bioorthogonal cleavage for in situ protein function restoration.
- Demonstrated application in protein activation and modulation of protein-protein interactions, including a "gated" anti-CD3 antibody.
Main Results:
- Successfully implemented CAGE-Proxvivo for precise, on-demand protein activation in living mice.
- Showcased the ability to modulate protein-protein interactions, exemplified by chemically regulated T cell activation.
- Demonstrated broad applicability across various biological contexts and phenotypes.
Conclusions:
- CAGE-Proxvivo provides a universal and versatile platform for controlling protein activity and interactions in vivo.
- This strategy facilitates time-resolved biological investigations and opens avenues for targeted therapeutic interventions.
