In vivo mRNA delivery to virus-specific T cells by light-induced ligand exchange of MHC class I antigen-presenting nanoparticles
Year: 2022
Type: article
Abstract: Simultaneous delivery of mRNA to multiple populations of antigen (Ag)-specific CD8 + T cells is challenging given the diversity of peptide epitopes and polymorphism of class I major histocompatibility complexes (MHCI). We developed Ag-presenting nanoparticles (APNs) for mRNA delivery using pMHCI molecules that were refolded with photocleavable peptides to allow rapid ligand exchange by UV light and site-specifically conjugated with a lipid tail for post-insertion into preformed mRNA lipid nanoparticles. Across different TCR transgenic mouse models (P14, OT-1, Pmel), UV-exchanged APNs bound and transfected their cognate Ag-specific CD8 + T cells equivalent to APNs produced using conventionally refolded pMHCI molecules. In mice infected with PR8 influenza, multiplexed delivery of UV-exchanged APNs against three immunodominant epitopes led to ~50% transfection of a VHH mRNA reporter in cognate Ag-specific CD8+ T cells. Our data shows that UV-mediated peptide exchange can be used to rapidly produce APNs for mRNA delivery to multiple populations of Ag-specific T cells in vivo . Teaser Light-induced rapid production of antigen-presenting nanoparticles for mRNA delivery to multiple virus-specific T cell populations.
Source: Science Advances
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: National Science Foundation, Burroughs Wellcome Fund, Alfred P. Sloan Foundation, Georgia Institute of Technology, Shurl and Kay Curci Foundation, Peking University, National Institutes of Health, Defense Advanced Research Projects Agency, Advanced Research Projects Agency, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, Division of Graduate Education, Division of Electrical, Communications and Cyber Systems, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1057711716, G1591029928, G2317904992, G2920422792, Graduate Research Fellowship Program (GRFP), IGERT: Stem Cell BIomanufacturing, G3824688650, G500973873, Noninvasive and predictive biomarkers of organ transplant rejection, G524204816, G5465412986, G5520316217, NNCI: Southeastern Nanotechnology Infrastructure Corridor (SENIC), G5927359219, G6021952647, G6076935313, G6823900908, Graduate Research Fellowship Program (GRFP), G790860305, Harnessing protease activity for predictive monitoring of cancer immunotherapy, G9000333168, T32 CTEng (Cellular and Tissue Engineering) Training Program
OpenAlex ID: W4220707673