Multi-pass membrane proteins — including G protein-coupled receptors (GPCRs), transporters, and claudins/tight junction proteins — represent a critically underserved
class of therapeutic targets. Their complex topology, hydrophobic transmembrane domains, and conformational dependence on a lipid bilayer environment render traditional recombinant protein immunization strategies largely ineffective. Soluble ectodomains and detergent-extracted preparations fail to present native epitopes, resulting in poor immune responses, low hit rates, and antibodies that lack functional activity against cell-surface antigen. We describe the NovoiSMART® mRNA-LNP immunization platform, a purpose-built solution for generating high-quality, functionally relevant antibody responses against multi-pass membrane protein targets. By delivering target-encoding mRNA formulated in lipid nanoparticles (LNPs), NovoiSMART® drives in vivo expression of full-length membrane proteins in their native conformation, circumventing the need for antigen purification and preserving conformationally sensitive epitopes critical for therapeutic antibody discovery.