{"doi":"10.1002/9783527838394.ch3","title":"Modified or Unmodified <scp>mRNA</scp> Vaccines? – The Biochemistry of Pseudouridine and <scp>mRNA</scp> Pseudouridylation","abstract":"It is estimated that COVID-19 vaccines have saved more than 20 million lives. The mRNA-based vaccines played a pivotal role. While some argued that this new therapeutic modality was developed too fast (it was deployed in less than 12 months for COVID-19), its success was, in fact, due to decades of intensive research performed at both academic and biotech labs. Efforts on developing the mRNA platform were focused on perfecting several enabling technologies for this modality, two of which proved to be highly critical in accelerating the development of the mRNA vaccines. These two technologies include lipid nanoparticle (LNP) formulations and the modified nucleoside pseudouridine (Ψ) (and its derivative N1-methyl-Ψ), the latter of which plays an essential role in reducing mRNA's inherent immunogenicity and increasing mRNA stability and protein production. This review will discuss the fundamentals of the biochemistry of this RNA modification, the biological impact of mRNA pseudouridylation, and its role in effective mRNA COVID-19 vaccines. We will also discuss some differences between pseudouridine-modified and -unmodified mRNA vaccines.","journal":null,"year":2024,"id":492557,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.9511,"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":317558,"name":"Yi‐Tao Yu","orcid":"0000-0003-2368-2799","position":1,"is_corresponding":false},{"id":317557,"name":"Pedro Morais","orcid":"0000-0001-8249-4312","position":0,"is_corresponding":true}],"reference_count":191,"raw_metadata":null,"created_at":"2026-07-19T02:08:56.210382Z","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":[]}