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<p>The management of inflammatory bowel disease (IBD) remains challenging, primarily due to the insufficient precision and efficacy of existing therapies. Consequently, there is an urgent need to develop novel treatment approaches. Here, we developed a therapeutic approach to generate epithelial cells with enhanced efferocytic capacity in vivo by delivering mRNA in lipid nanoparticles (LNPs). We demonstrated that LNPs-mediated delivery of mRNA enables functional editing of epithelial cells in vitro and in vivo, and our findings suggest that enhanced efferocytosis in engineered epithelial cells may contribute to inflammation resolution and restoration of tissue homeostasis. In murine models of colitis, intraperitoneal administration of mRNA-loaded nanoparticles designed to boost efferocytosis markedly attenuated intestinal inflammation and halted disease progression. This strategy provides a proof of concept that epithelial cells can be functionally engineered in situ and represents a promising therapeutic avenue for mitigating inflammatory tissue damage.</p>

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In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice

  • 期刊论文

  • 发表日期：

    2026年5月19日

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  • Hailing Zhang,
  • Hengxing Lu,
  • Shaolong Zhang,
  • Xukai Hu,
  • Qixin Wu,
  • Ziqin Yu,
  • Natasha Karyn Lienanto,
  • Jin Zhang

摘要

The management of inflammatory bowel disease (IBD) remains challenging, primarily due to the insufficient precision and efficacy of existing therapies. Consequently, there is an urgent need to develop novel treatment approaches. Here, we developed a therapeutic approach to generate epithelial cells with enhanced efferocytic capacity in vivo by delivering mRNA in lipid nanoparticles (LNPs). We demonstrated that LNPs-mediated delivery of mRNA enables functional editing of epithelial cells in vitro and in vivo, and our findings suggest that enhanced efferocytosis in engineered epithelial cells may contribute to inflammation resolution and restoration of tissue homeostasis. In murine models of colitis, intraperitoneal administration of mRNA-loaded nanoparticles designed to boost efferocytosis markedly attenuated intestinal inflammation and halted disease progression. This strategy provides a proof of concept that epithelial cells can be functionally engineered in situ and represents a promising therapeutic avenue for mitigating inflammatory tissue damage.