In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice

Abstract

Engineered epithelial cells with enhanced efferocytosis capacity promote inflammation resolution and restore tissue homeostasis. Here, we developed a therapeutic approach to generate efferocytosis boosting epithelial cells in vivo by delivering mRNA in lipid nanoparticles (LNPs). We demonstrate that LNP-mediated delivery of mRNA enables efficient in vitro and in vivo functional editing of epithelial cells. 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 functional engineered in situ and represents a promising therapeutic avenue for mitigating inflammatory tissue damage. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/678706v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@874991org.highwire.dtl.DTLVardef@1eefbfforg.highwire.dtl.DTLVardef@e22fa6org.highwire.dtl.DTLVardef@1a6480d_HPS_FORMAT_FIGEXP M_FIG C_FIG