{"doi":"10.1101/2021.10.14.464373","title":"<i>In vivo</i> mRNA delivery to virus-specific T cells by light-induced ligand exchange of MHC class I antigen-presenting nanoparticles","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221881,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822457,"name":"Qingyang Henry Zhao","orcid":"0000-0002-6757-7504","position":1,"is_corresponding":false},{"id":816601,"name":"Shreyas N. Dahotre","orcid":null,"position":2,"is_corresponding":false},{"id":509798,"name":"Lena Gamboa","orcid":"0000-0003-1424-3604","position":3,"is_corresponding":false},{"id":621418,"name":"Swapnil Bawage","orcid":"0000-0001-9139-5375","position":4,"is_corresponding":false},{"id":769486,"name":"Aaron D. Silva Trenkle","orcid":"0000-0001-9331-6191","position":5,"is_corresponding":false},{"id":509799,"name":"Ali Zamat","orcid":"0000-0001-5751-6508","position":6,"is_corresponding":false},{"id":565867,"name":"Hathaichanok Phuengkham","orcid":"0000-0003-4083-2752","position":7,"is_corresponding":false},{"id":226172,"name":"Rafi Ahmed","orcid":"0000-0002-9591-2621","position":8,"is_corresponding":false},{"id":320918,"name":"Philip J. Santangelo","orcid":"0000-0001-7352-0339","position":9,"is_corresponding":false},{"id":497869,"name":"Gabriel A. Kwong","orcid":"0000-0002-6255-6755","position":10,"is_corresponding":false},{"id":374174,"name":"Fang‐Yi Su","orcid":"0000-0003-2852-161X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:59.302331Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}