期刊
SCIENCE ADVANCES
卷 8, 期 8, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abm7950
关键词
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资金
- Defense Advanced Research Projects Agency [HR00111920008]
- NIH [DP2HD091793, R01CA237210-01]
- NSF [ECCS-1542174]
- Burroughs Wellcome Fund, Career Award at the Scientific Interface
- NSF Graduate Research Fellowships Program [DGE-1650044, DGE-1451512, DGE-2039655]
- NSF Integrative Graduate Education and Research Traineeship [DGE-0965945]
- Alfred P. Sloan Foundation
- NIH GTBioMAT Training Grant [5T32EB006343]
- NIH Cell and Tissue Engineering (CTEng) Training Program [5T32GM8433-30]
- Georgia Tech President's Fellowship
In this study, we developed Ag-presenting nanoparticles (APNs) for mRNA delivery to multiple populations of antigen-specific CD8(+) T cells using UV-mediated peptide exchange and site-specific conjugation with lipid tails. The data demonstrate the successful transfection of cognate Ag-specific CD8(+) T cells with UV-exchanged APNs.
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 postinsertion into preformed mRNA lipid nanoparticles. Across different TCR transgenic mouse models (P14, OT-1, and 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, multi-plexed delivery of UV-exchanged APNs against three immunodominant epitopes led to similar to 50% transfection of a VHH mRNA reporter in cognate Ag-specific CD8(+) T cells. Our data show 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.
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