Fig. 1. Schematic of UV-mediated peptide exchange of MHCI APNs for in vivo multiplexed delivery to virus-specific T cells.

(A) We refold pMHC molecules with photolabile peptides and then conjugated them to a lipid tail to allow subsequent formulation with preformed lipid nanoparticles (NPs). The presence of UV light cleaves the photolabile peptide and induces replacement of the resulting empty MHC groove with a library of viral peptides. After the UV-mediated peptide ligand exchange, we functionalize pMHC molecules on the surface of preformed LNPs via postinsertion to form the APN library for multiplexed delivery to virus-specific T cells. (B) After intravenous injection into living mice, APNs selectively target cognate T cell populations and transfect them with model mRNA. We validate the mRNA expression using flow analysis.