{"doi":"10.1021/jacs.3c05574","title":"A Unified Strategy to Improve Lipid Nanoparticle Mediated mRNA Delivery Using Adenosine Triphosphate","abstract":"A central goal of chemical and drug delivery sciences is to maximize the therapeutic efficacy of a given drug at the lowest possible dose. Here, we report a generalizable strategy that can be utilized to improve the delivery of mRNA drugs using lipid nanoparticles (LNPs), the clinically approved chemistry platforms utilized in the Moderna and Pfizer/BioNTech COVID-19 vaccines. In brief, our strategy updates the chemistry of LNPs to incorporate adenosine triphosphate (ATP) alongside mRNA, a modification that results in upward of a 79-fold increase in LNP-delivered mRNA-encoded protein expression in vitro and a 24-fold increase in vivo when compared to parent mRNA LNP formulations that do not contain ATP. Notably, we find that our ATP co-delivery strategy increases LNP-delivered mRNA-encoded protein expression across eight different LNP chemistries and three different cell lines, under normoxia and hypoxia, and in a well-tolerated fashion. Notably, our strategy also improves the expression of mRNA encoding for intracellular and secreted proteins both in vitro and in vivo, highlighting the utility of leveraging ATP co-delivery within mRNA LNPs as a means to increase protein expression. In developing this strategy, we hope that we have provided a simple yet powerful approach to improving mRNA LNPs that may one day be useful in developing therapies for human disease.","journal":"Journal of the American Chemical Society","year":2023,"id":320840,"datarank":1.1878194964899784,"base_score":3.8918202981106265,"endowment":3.8918202981106265,"self_citation_contribution":0.5837730447165941,"citation_network_contribution":0.6040464517733843,"self_endowment_contribution":0.5837730447165941,"citer_contribution":0.6040464517733843,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":30,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1032153,"name":"Owen S. Fenton","orcid":"0000-0002-5585-9280","position":1,"is_corresponding":false},{"id":1032152,"name":"Yutian Ma","orcid":"0000-0002-0110-0244","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:07:27.434133Z","pmid":"37656876","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":[]}