In vivo mRNA delivery to virus-specific T cells by light-induced ligand exchange of MHC class I antigen-presenting nanoparticles

被引：41

作者：

Su, Fang-Yi ^{[1
,2
]}

Zhao, Qingyang Henry ^{[1
,2
]}

Dahotre, Shreyas N. ^{[1
,2
]}

Gamboa, Lena ^{[1
,2
]}

Bawage, Swapnil Subhash ^{[1
,2
]}

Trenkle, Aaron D. Silva ^{[1
,2
]}

Zamat, Ali ^{[1
,2
]}

Phuengkham, Hathaichanok ^{[1
,2
]}

Ahmed, Rafi ^{[3
,4
,5
]}

Santangelo, Philip J. ^{[1
,2
]}

Kwong, Gabriel A. ^{[1
,2
,5
,6
,7
,8
,9
,10
]}

机构：

[1] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA

[2] Emory Univ, Atlanta, GA 30322 USA

[3] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30317 USA

[4] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

[5] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[6] Georgia Inst Technol, Inst Elect & Nanotechnol, Atlanta, GA 30332 USA

[7] Georgia Inst Technol, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA

[8] Integrated Canc Res Ctr, Georgia Inst Technol, Atlanta, GA 30332 USA

[9] Emory Univ, Georgia ImmunoEngn Consortium, Atlanta, GA 30332 USA

[10] Georgia Inst Technol, Atlanta, GA 30332 USA

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 08期

关键词：

LYMPHOCYTIC CHORIOMENINGITIS VIRUS; PEPTIDE EXCHANGE; REPERTOIRE; COMPLEXES; RESPONSES; PROTEIN; EPITOPE;

D O I：

10.1126/sciadv.abm7950

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 67 条

[1] Site-Specific Antibody-Drug Conjugates: The Nexus of Biciorthogonal Chemistry, Protein Engineering, and Drug Development [J].