Scholarlink

<p>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, Ca<sup>2+</sup> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月22日

查看全文
  • Yaqing Si,
  • Minghui He,
  • Yilin Li,
  • Jian Jiang,
  • Yuxuan Fan,
  • Shuai Xue,
  • Xinyuan Qiu,
  • Mingqi Xie

摘要

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.