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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.

2025-10-10 bioengineering
10.1101/2025.10.08.678706 bioRxiv
Show 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

Published in Inflammation Research · not in our set (fewer than 10 published preprints to learn from) · training set

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The top 7 journals account for 50% of the predicted probability mass.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.