On-demand treatment of metabolic diseases by a synthetic drug-inducible exocytosis system

Yaqing Si, Minghui He, Yilin Li, Jian Jiang, Yuxuan Fan, Shuai Xue, Xinyuan Qiu and Mingqi Xie ()
Additional contact information
Yaqing Si: Fudan University
Minghui He: Fudan University
Yilin Li: Westlake Laboratory of Life Sciences and Biomedicine
Jian Jiang: Westlake Laboratory of Life Sciences and Biomedicine
Yuxuan Fan: Westlake Laboratory of Life Sciences and Biomedicine
Shuai Xue: Westlake Laboratory of Life Sciences and Biomedicine
Xinyuan Qiu: National University of Defense Technology
Mingqi Xie: Westlake Laboratory of Life Sciences and Biomedicine

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Here, we present StimExo as a rational design strategy allowing various user-defined control signals to trigger calcium-dependent exocytosis and mediate on-demand protein secretion in cell-therapy settings. Using a modular framework incorporating inducible protein-protein interactions into an engineered bipartite activator of calcium release–activated calcium (CRAC) channels, Ca2+ influx mediated by the STIM/Orai1 machinery was flexibly adjusted to depend on different user-defined input signals. Application of StimExo to various endocrine cells enables instant secretion of therapeutic hormones upon administration of safe and patient-compliant trigger compounds. StimExo also mediated insulin exocytosis using a cell-based gene delivery strategy in vivo, accounting for real-time control of blood glucose homeostasis in male diabetic mice in response to the FDA-approved drug grazoprevir. This study achieves true “sense-and-respond” cell-based therapies and provides a platform for remote control of in vivo transgene activities using various trigger signals of interest.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58184-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58184-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58184-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().