Gastrointestinal\nDevice-Mediated Delivery of mRNA-Lipid\nNanoparticles Achieves Distinct Expression and Biodistribution in\nMice and Pigs

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