In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice.

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.