In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice

Area of Science:

• Gastroenterology
• Cellular Biology
• Nanomedicine

Background:

• Inflammatory bowel disease (IBD) management is challenging due to limited precision and efficacy of current treatments.
• Novel therapeutic strategies are urgently needed to address IBD's complexities.

Purpose of the Study:

• To develop a therapeutic approach for enhancing epithelial cell efferocytic capacity in vivo.
• To investigate the potential of mRNA-delivered lipid nanoparticles (LNPs) for in situ epithelial cell engineering.

Main Methods:

• Utilized lipid nanoparticles (LNPs) for in vivo delivery of mRNA to epithelial cells.
• Engineered epithelial cells for enhanced efferocytosis.
• Administered mRNA-loaded nanoparticles in murine models of colitis.

Main Results:

• Demonstrated successful functional editing of epithelial cells in vitro and in vivo using LNPs.
• Observed that enhanced efferocytosis in engineered cells may aid inflammation resolution and tissue homeostasis.
• Markedly attenuated intestinal inflammation and halted disease progression in colitis models.

Conclusions:

• Epithelial cells can be functionally engineered in situ using mRNA-loaded LNPs.
• This strategy offers a promising therapeutic avenue for mitigating inflammatory tissue damage in IBD.
• Enhanced efferocytosis presents a viable mechanism for resolving inflammation and restoring tissue balance.