Gastrointestinal Device-Mediated Delivery of mRNA-Lipid Nanoparticles Achieves Distinct Expression and Biodistribution in Mice and Pigs

Recent investigations into autonomous ingestible microjet devices have demonstrated the feasibility of delivering many drug modalities directly into the gastrointestinal (GI) wall via the oral route. However, the expression and biodistribution of mRNA after such injections remain unexplored. mRNA-lipid nanoparticles (mRNA-LNPs) are promising therapeutics for treating or vaccinating against many diseases and pathogens. Today, mRNA-LNPs are given as injections, necessitating trained medical personnel and resulting in reduced patient compliance. Here, we elucidate the expression and biodistribution of mRNA-LNPs after injection into the gastric and intestinal walls of mice and minipigs. We see a controlled release of mRNA from the stomach and intestine with mRNA in both plasma and lymph nodes, leading to a broad biodistribution profile, which could lead to better immunization after vaccination. Our results substantiate the argument that ingestible microjet devices facilitate a viable route of administration for use as an alternative to injections of mRNA-LNP.