Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41722565.
- Also identified by DOI 10.1016/j.xcrm.2026.102634 and PMC identifier 13006438.
- Licence recorded as CC BY-NC-ND.
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Abstract
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.
Medical subject headings
- Insulin-Secreting Cells
- Nanoparticles
- RNA, Messenger
- Lipids