Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer.

ABSTRACT: Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry and administration routes may enable mRNA-induced protein expression outside of the reticuloendothelial system. Here, we describe a strategy for delivering mRNA potently and specifically to the pancreas using lipid nanoparticles. Our results show that delivering lipid nanoparticles containing cationic helper lipids by intraperitoneal administration produces robust and specific protein expression in the pancreas. Most resultant protein expression occurred within insulin-producing β cells. Last, we found that pancreatic mRNA delivery was dependent on horizontal gene transfer by peritoneal macrophage exosome sec

SUBMITTER: Melamed JR 

PROVIDER: S-EPMC9882987 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature