Researchers at Texas A&M University engineered nanobodies integrated with self-cleaving viral proteases to control protein function directly inside living cells, according to a study published in Nature Communications. The system, termed VIPbodies, converts viral protease inhibition into drug-dependent antigen recognition.
The research team tested the approach using anti-mCherry nanobodies as prototypes before expanding the design across diverse nanobody scaffolds. The resulting VIPbody variants respond to orthogonal viral protease-inhibitor pairs. Because each VIPbody operates independently within the same cell, the framework enables multiplexed regulation of distinct target proteins.
When incorporated into transcriptional circuits, VIPbodies mediate drug-tunable gene expression and execute all six canonical Boolean logic operations. The authors demonstrated that VIPbody circuits extend beyond gene control to achieve chemogenetic control over cell fate. The circuits provide bidirectional control of pyroptosis and selectively activate either apoptotic or pyroptotic cellular programs through caspase coupling.
The project involved researchers across the Center for Translational Cancer Research, the Center for Epigenetics and Disease Prevention, and the Department of Translational Medical Sciences at Texas A&M University in Houston. Equal contributions were made by Mingguang Cui, Xiaoxuan Liu, and Tien-Hung Lan, alongside co-authors Tianlu Wang, Tatsuki Nonomura, Brendan McKee, Rui Wang, Yun Huang, and Yubin Zhou.
Yubin Zhou, Yun Huang, Mingguang Cui, and Tien-Hung Lan filed a U.S. Patent and Trademark Office application, number 64/115,275, regarding the design and biomedical applications of the technology. The research received support from the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, the Welch Foundation, and Blood Cancer United, formerly the Leukemia and Lymphoma Society. Nature Communications received the manuscript on Dec. 4, 2025, accepted it on July 21, 2026, and published it on July 30, 2026.
