{"doi":"10.1126/sciadv.aba2422","title":"Single-dose mRNA therapy via biomaterial-mediated sequestration of overexpressed proteins","abstract":"Nonviral mRNA delivery is an attractive therapeutic gene delivery strategy, as it achieves efficient protein overexpression in vivo and has a desirable safety profile. However, mRNA's short cytoplasmic half-life limits its utility to therapeutic applications amenable to repeated dosing or short-term overexpression. Here, we describe a biomaterial that enables a durable in vivo response to a single mRNA dose via an \"overexpress and sequester\" mechanism, whereby mRNA-transfected cells locally overexpress a growth factor that is then sequestered within the biomaterial to sustain the biologic response over time. In a murine diabetic wound model, this strategy demonstrated improved wound healing compared to delivery of a single mRNA dose alone or recombinant protein. In addition, codelivery of anti-inflammatory proteins using this biomaterial eliminated the need for mRNA chemical modification for in vivo therapeutic efficacy. The results support an approach that may be broadly applicable for single-dose delivery of mRNA without chemical modification.","journal":"Science Advances","year":2020,"id":95958,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":402733,"name":"Xiaohua Yu","orcid":"0000-0002-0233-0121","position":1,"is_corresponding":false},{"id":476451,"name":"Jennifer M. Umhoefer","orcid":"0000-0002-8563-9641","position":2,"is_corresponding":false},{"id":443985,"name":"Connie S. Chamberlain","orcid":"0000-0002-4980-4347","position":3,"is_corresponding":false},{"id":476452,"name":"Linzie A. Wildenauer","orcid":"0000-0002-8843-7973","position":4,"is_corresponding":false},{"id":477843,"name":"Gaoussou M. Diarra","orcid":null,"position":5,"is_corresponding":false},{"id":476453,"name":"Timothy A. Hacker","orcid":"0000-0003-1473-1325","position":6,"is_corresponding":false},{"id":395184,"name":"William L. Murphy","orcid":"0000-0001-5577-7739","position":7,"is_corresponding":false},{"id":307121,"name":"Andrew Khalil","orcid":"0000-0003-1526-6656","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T22:34:34.781847Z","pmid":"32937431","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":[]}