Effective treatment for type 1 diabetes (T1D) must both suppress excessive immune activity and reduce the susceptibility of β cells to damage. We describe a lipid nanoparticle (LNP) platform for β cell-enriched mRNA delivery, which is further enhanced by combining with enhanced glucagon-like peptide-1 (eGLP-1). Both non-conjugated and eGLP-conjugated LNP can efficiently deliver mRNA to mouse and human β cells in vitro. In vivo biodistribution studies of C57BL/6J mice showed that LNP exhibited outstanding enrichment in the pancreas, and eGLP-LNPs achieved more β cell enrichment in mice compared to un-conjugated LNP. In pre-diabetic NOD mice, LNP delivery of PD-L1 mRNA can induce PD-L1 expression in β cells, alleviate islet inflammation, and delay the onset of autoimmune diabetes. Importantly, we found that LNP can also deliver mRNA to human β cells in the allogeneic islet transplantation model in vivo. These findings collectively establish a multifunctional and translationally relevant LNP platform for β cell-oriented mRNA delivery and immune regulation of T1D.
This study was published under the title "Delivery of Messenger RNA to Islet β Cells Using Conjugated Lipid Nanoparticles" in Cell Reports Medicine.
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DOI: 10.1016/j.xcrm.2026.102634