{"doi":"10.3389/fddev.2024.1359700","title":"Single cell phototransfection of mRNAs encoding SARS-CoV2 spike and nucleocapsid into human astrocytes results in RNA dependent translation interference","abstract":"Multi-RNA co-transfection is starting to be employed to stimulate immune responses to SARS-CoV-2 viral infection. While there are good reasons to utilize such an approach, there is little background on whether there are synergistic RNA-dependent cellular effects. To address this issue, we use transcriptome-induced phenotype remodeling (TIPeR) via phototransfection to assess whether mRNAs encoding the Spike and Nucleocapsid proteins of SARS-CoV-2 virus into single human astrocytes (an endogenous human cell host for the virus) and mouse 3T3 cells (often used in high-throughput therapeutic screens) synergistically impact host cell biologies. An RNA concentration-dependent expression was observed where an increase of RNA by less than 2-fold results in reduced expression of each individual RNAs. Further, a dominant inhibitory effect of Nucleocapsid RNA upon Spike RNA translation was detected that is distinct from codon-mediated epistasis. Knowledge of the cellular consequences of multi-RNA transfection will aid in selecting RNA concentrations that will maximize antigen presentation on host cell surface with the goal of eliciting a robust immune response. Further, application of this single cell stoichiometrically tunable RNA functional genomics approach to the study of SARS-CoV-2 biology promises to provide details of the cellular sequalae that arise upon infection in anticipation of providing novel targets for inhibition of viral replication and propagation for therapeutic intervention.","journal":"Frontiers in Drug Delivery","year":2024,"id":461921,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9639,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1291386,"name":"Quentin Brosseau","orcid":null,"position":1,"is_corresponding":false},{"id":1291387,"name":"Julia Radzio","orcid":null,"position":2,"is_corresponding":false},{"id":415524,"name":"Jinhui Wang","orcid":"0000-0001-8340-717X","position":3,"is_corresponding":false},{"id":20749,"name":"Hiromi Muramatsu","orcid":"0000-0003-1544-1493","position":4,"is_corresponding":false},{"id":522368,"name":"Da Kuang","orcid":"0000-0003-3554-0464","position":5,"is_corresponding":false},{"id":491213,"name":"M. Sean Grady","orcid":null,"position":6,"is_corresponding":false},{"id":814057,"name":"H. Isaac Chen","orcid":"0000-0001-6122-4743","position":7,"is_corresponding":false},{"id":227217,"name":"John A. Wolf","orcid":"0000-0002-6950-2303","position":8,"is_corresponding":false},{"id":373444,"name":"Alexandra V. Ulyanova","orcid":"0000-0002-1319-5279","position":9,"is_corresponding":false},{"id":526488,"name":"Tamás Bartfai","orcid":null,"position":10,"is_corresponding":false},{"id":251905,"name":"Junhyong Kim","orcid":"0000-0002-7726-8246","position":11,"is_corresponding":false},{"id":54904,"name":"Norbert Pardi","orcid":"0000-0003-1008-6242","position":12,"is_corresponding":false},{"id":753308,"name":"Jai‐Yoon Sul","orcid":"0000-0001-6788-1103","position":13,"is_corresponding":false},{"id":790997,"name":"Paulo E. Arratia","orcid":"0000-0002-2566-2663","position":14,"is_corresponding":false},{"id":283959,"name":"James Eberwine","orcid":"0000-0002-9363-0858","position":15,"is_corresponding":false},{"id":761453,"name":"Hyun‐Bum Kim","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:04:16.410510Z","pmid":"40836990","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":[]}