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Updated: Feb 23, 2026
10:02
Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
Published on: June 10, 2022
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Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles
Jacob R Enriquez1, Zhengjie Zhou2, Jennifer B Nelson1
1Kovler Diabetes Center and Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, IL, USA.
Cell Reports. Medicine
|February 21, 2026
Summary
A novel lipid nanoparticle (LNP) platform effectively delivers mRNA to pancreatic beta cells, showing promise for type 1 diabetes (T1D) treatment by modulating immune responses and protecting beta cells.
Area of Science:
- Biotechnology
- Immunology
- Endocrinology
Background:
- Type 1 diabetes (T1D) requires therapies that suppress immune attacks and protect pancreatic beta cells.
- Current T1D treatments face challenges in targeting specific cells and modulating immune responses effectively.
Purpose of the Study:
- To develop and evaluate a lipid nanoparticle (LNP) platform for targeted messenger RNA (mRNA) delivery to pancreatic beta cells.
- To enhance beta cell targeting using conjugation with enhanced glucagon-like peptide-1 (eGLP-1).
- To assess the therapeutic potential of this LNP platform in preclinical models of T1D.
Main Methods:
- Development of LNP formulations for mRNA delivery, including eGLP-1 conjugated variants.
- In vitro assessment of LNP efficiency in delivering mRNA to mouse and human beta cells.
- In vivo biodistribution studies in C57BL/6J mice to evaluate pancreatic and beta cell enrichment.
- Testing LNP-mediated PD-L1 mRNA delivery in prediabetic NOD mice to assess immune modulation and diabetes onset.
- Evaluation of LNP delivery to human beta cells in a xenogeneic islet transplantation model.
Main Results:
- Both unconjugated and eGLP-conjugated LNPs demonstrated efficient mRNA delivery to beta cells in vitro.
- In vivo studies showed pancreatic enrichment of LNPs, with eGLP-LNPs achieving greater beta cell specificity in mice.
- LNP delivery of PD-L1 mRNA in NOD mice attenuated insulitis and delayed autoimmune diabetes onset.
- LNPs successfully delivered mRNA to human beta cells within a xenograft model, indicating translational potential.
Conclusions:
- A versatile LNP platform for targeted mRNA delivery to beta cells has been established.
- eGLP-1 conjugation enhances LNP accumulation in pancreatic beta cells.
- This LNP platform shows potential for immune modulation and therapeutic intervention in type 1 diabetes.
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