2026-02-25 シカゴ大学（UChicago）
＜関連情報＞
- https://news.uchicago.edu/story/new-tech-shows-promise-engineering-cells-prevent-type-1-diabetes
- https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00051-0
結合脂質ナノ粒子を用いた膵島β細胞へのメッセンジャーRNA送達 Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles
Jacob R. Enriquez ∙ Zhengjie Zhou ∙ Jennifer B. Nelson ∙ … ∙ Sarah A. Tersey ∙ Yun Fang, ∙ Raghavendra G. Mirmira
Cell Reports Medicine Published:February 20, 2026
DOI:https://doi.org/10.1016/j.xcrm.2026.102634
Graphical abstract
Highlights
- eGLP-conjugated lipid nanoparticles enhance β cell-enriched targeting
- Lipid nanoparticles deliver functional mRNA to mouse and human β cells
- PD-L1 mRNA is delivered to human β cells in vivo after LNP administration
- β cell PD-L1 expression delays autoimmune diabetes in NOD mice
Summary
Effective therapies for type 1 diabetes (T1D) must both restrain immune hyperactivity and reduce β cell susceptibility to destruction. We describe a lipid nanoparticle (LNP) platform for β cell-enriched mRNA delivery that can be further augmented by conjugation to enhanced glucagon-like peptide-1 (eGLP-1). Both unconjugated and eGLP-conjugated LNPs deliver mRNA efficiently to mouse and human β cells in vitro. Biodistribution studies in C57BL/6J mice in vivo demonstrate pancreatic enrichment of LNPs, with greater β cell enrichment achieved by eGLP-LNPs compared with unconjugated LNPs specifically in mice. In prediabetic NOD mice, LNP delivery of PD-L1 mRNA induces β cell PD-L1 expression, attenuates insulitis, and delays the onset of autoimmune diabetes. Importantly, we find that LNPs also deliver mRNA to human β cells in a xenogeneic islet transplantation model in vivo. Together, these findings establish a versatile and translationally relevant LNP platform for β cell-directed mRNA delivery and immune modulation in T1D.
