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bioRxiv · 10.1101/2025.10.08.678706

In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice

Zhang, H.·Lu, H.·Zhang, S.·Hu, X.·Wu, Q.·Yu, Z.·Lienanto, N. K.·Zhang, J.
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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

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Zhang, H., Lu, H., Zhang, S., Hu, X., Wu, Q., Yu, Z., Lienanto, N. K., Zhang, J.. 2025-10-10. In vivo colonic epithelial cell editing attenuates intestinal inflammation in mice. https://doi.org/10.1101/2025.10.08.678706

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