Xin Wang, Yuan Liu, Zhenchao Wang, Xiangmei Zeng, William Shu Ching Ngai, Jie Wang, Heng Zhang, Xiao Xie, Rongfeng Zhu, Xinyuan Fan, Chu Wang, Peng R. Chen
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引用次数: 0
Abstract
A universal strategy to precisely control protein activation in living animals is crucial for gain-of-function study of proteins under in vivo settings. We herein report CAGE-Proxvivo, a computer-aided proximal decaging strategy for on-demand protein activation as well as protein-protein interaction modulations in living mice. Through machine-learning-assisted evolution of desired aminoacyl-tRNA synthetases (aaRSs), we successfully incorporated chemically caged amino acids into rationally designed “decaging sites” to transiently block target proteins’ function, which can be restored in situ via a small-molecule-triggered bioorthogonal cleavage reaction. This method demonstrates broad applicability ranging from activating proteins of interest to cell-type-specific modulation of distinct phenotypes in living systems. Beyond the active-pocket decaging, CAGE-Proxvivo also enables precise control of protein-protein interactions, as exemplified by a “gated” anti-CD3 antibody that permits chemically regulated T cell recruitment and activation at tumor sites. Overall, CAGE-Proxvivo offers a universal platform for time-resolved biological studies and on-demand therapeutic interventions under living conditions.
期刊介绍:
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.