Versatility of LNPs across different administration routes for targeted RNA delivery

The advent of lipid nanoparticle (LNP) technology has marked a significant breakthrough in the field of drug delivery, offering unprecedented opportunities in gene therapy, vaccine delivery, and personalized medicine. The use and effectiveness of LNPs greatly depend on their optimization, often tailored to specific routes of administration. Different routes can significantly influence organ distribution, expression kinetics and therapeutic outcomes of LNPs, with the choice of the route dependent on LNP properties, target sites, and therapeutic indications. In this review, we summarize recent studies that highlight the versatility of LNPs, through optimization for delivery across different routes of administration, while scrutinizing the route-dependent formulation strategies. We then outline key challenges facing LNP optimization for site-specific RNA administration and propose future prospects for employing appropriate administration routes to develop LNP-based RNA medicines.