Cell-specific mRNA delivery via nanobody-functionalized lipid nanoparticles

-TCO via a two-step click chemistry (SPAAC and IEDDA) reaction. Our findings demonstrate that APN-targeted, mRNA-loaded LNPs selectively target APN-expressing cells, enhancing LNP uptake and mRNA delivery to these cells. Furthermore, we show that directing the nanobody-functionalized mRNA-LNPs toward APN promotes their transcytosis across the gut epithelial barrier in porcine apical-out intestinal organoids and in vivo. Together, these findings highlight the potential of this programmable platform for the cell-specific delivery of mRNA-based vaccines and therapeutics. While this study focuses on porcine APN, the approach is adaptable across species, providing a versatile and customizable solution for the precise delivery of mRNA payloads to specific cells.