Anti-inflammation lipid nanoparticles enable localized mRNA therapy for inflammatory bowel disease
Abstract
Inflammatory bowel disease (IBD) is an incurable disorder that requires long-term management, which is limited by suboptimal efficacy and systemic toxicity of current treatments. We developed a series of glucocorticoid-derived ionizable lipids and formulated them into lipid nanoparticles (LNPs) for rectal and lesion-localized mRNA delivery. MP2 LNPs, the lead formulation based on a methylprednisolone-derived ionizable lipid, showed a 15-fold higher delivery efficiency in vivo than the FDA approved SM102 LNPs. When loaded with interleukin-35 (IL-35) mRNA, MP2 LNPs (MP2-IL-35) ameliorated colitis in acute and chronic IBD mouse models, as shown by improved clinical scores, preserved colon length, and reduced pro-inflammatory cytokines. In ex vivo human colonic biopsies, MP2 LNPs enabled effective mRNA delivery in immune, epithelial and endothelial cells. Moreover, in biopsies from patients with IBD, MP2-IL-35 LNPs significantly reshaped effector and regulatory T cell subsets. Together, these findings support MP2-IL-35 LNPs as a promising mRNA therapy for IBD.
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BibTeX
@article{cao2026antiinflammation,
title = {{Anti-inflammation lipid nanoparticles enable localized mRNA therapy for inflammatory bowel disease}},
author = {Dinglingge Cao and Meng Tian and Changyue Yu and Yonger Xue and Zhengwei Liu and Yichen Zhong and Xucheng Hou and Haoyuan Li and Ya Ying Zheng and Siyu Wang and Michael Tankelevich and Shruti Naik and Saurabh Mehandru and Yizhou Dong},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78302-5},
url = {https://www.nature.com/articles/s41467-026-78302-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Anti-inflammation lipid nanoparticles enable localized mRNA therapy for inflammatory bowel disease
AU - Dinglingge Cao
AU - Meng Tian
AU - Changyue Yu
AU - Yonger Xue
AU - Zhengwei Liu
AU - Yichen Zhong
AU - Xucheng Hou
AU - Haoyuan Li
AU - Ya Ying Zheng
AU - Siyu Wang
AU - Michael Tankelevich
AU - Shruti Naik
AU - Saurabh Mehandru
AU - Yizhou Dong
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78302-5
UR - https://www.nature.com/articles/s41467-026-78302-5
AB - Inflammatory bowel disease (IBD) is an incurable disorder that requires long-term management, which is limited by suboptimal efficacy and systemic toxicity of current treatments. We developed a series of glucocorticoid-derived ionizable lipids and formulated them into lipid nanoparticles (LNPs) for rectal and lesion-localized mRNA delivery. MP2 LNPs, the lead formulation based on a methylprednisolone-derived ionizable lipid, showed a 15-fold higher delivery efficiency in vivo than the FDA approved SM102 LNPs. When loaded with interleukin-35 (IL-35) mRNA, MP2 LNPs (MP2-IL-35) ameliorated colitis in acute and chronic IBD mouse models, as shown by improved clinical scores, preserved colon length, and reduced pro-inflammatory cytokines. In ex vivo human colonic biopsies, MP2 LNPs enabled effective mRNA delivery in immune, epithelial and endothelial cells. Moreover, in biopsies from patients with IBD, MP2-IL-35 LNPs significantly reshaped effector and regulatory T cell subsets. Together, these findings support MP2-IL-35 LNPs as a promising mRNA therapy for IBD.
SN - 2041-1723
ER -