Lipid Nanoparticles Achieve Pancreatic-Targeted mRNA Delivery in Multiple Animal Models
Researchers developed pancreatic-targeted lipid nanoparticles (AH-LNP) that enable precise mRNA delivery to the pancreas through capsule-filter-mediated accumulation. The platform demonstrated efficacy in genome editing and cancer immunotherapy across multiple animal models including non-human primates.
Researchers have identified a universal principle for pancreatic-selective delivery and developed a pancreatic-targeted lipid nanoparticle (AH-LNP) for mRNA delivery. Achieving pancreatic-targeted delivery marks a breakthrough in treating pancreatic diseases, yet precise delivery has remained challenging.
AH-LNP exhibits size enlargement after assembly with proteins, facilitating capsule-filter-mediated pancreas-selective accumulation and receptor-mediated endocytosis, thereby boosting the pancreatic-targeted ability. The platform enables precise and efficient genome editing in the pancreas through the delivery of Cas9 mRNA and single guide RNA (sgRNA), exhibiting promising potential in the treatment of autoimmune pancreatic diseases.
Pancreatic-targeted delivery of mRNA encoding therapeutic cytokines through AH-LNP demonstrates superior antitumor efficacy when combined with a cancer vaccine or chimeric antigen receptor T cell therapy in multiple pancreatic cancer models. The safety and pancreatic mRNA delivery of AH-LNP were verified in multiple animal models, including non-human primates, demonstrating great promise for clinical translation.
The raw sequencing data reported in the study have been deposited at the Genome Sequence Archive under accession number PRJCA051840. Data for VLDLR expression across various organs in humans are accessible in the DISCO. Data on PD-L1 expression in pancreatic tumours and its correlation with survival are available in the GEPIA.
The findings highlight the transformative potential of this pancreatic-targeted mechanism and the derived LNP platform, opening avenues for developing precision therapeutics against diverse pancreatic diseases. mRNA-LNP therapy has emerged as a powerful strategy in treating various chronic diseases and cancers, holding promise in pancreatic diseases.