{"doi":"10.1002/humu.24116","title":"Rescue of common exon‐skipping mutations in cystic fibrosis with modified U1 snRNAs","abstract":null,"journal":"Human Mutation","year":2020,"id":604381,"datarank":0.6592476736280221,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.24335936529205485,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.24335936529205485,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":13,"citers_with_citation_signal":10,"citers_with_endowment":10,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1229615,"name":"Malgorzata Ewa Rogalska","orcid":"0000-0002-6331-9815","position":1,"is_corresponding":false},{"id":376673,"name":"Giulia Pianigiani","orcid":"0000-0003-0851-1473","position":2,"is_corresponding":false},{"id":1550639,"name":"Susana Igreja","orcid":"0000-0003-2811-4766","position":3,"is_corresponding":false},{"id":424065,"name":"Margarida D. Amaral","orcid":"0000-0002-0828-8630","position":4,"is_corresponding":false},{"id":1456755,"name":"Franco Pagani","orcid":"0000-0002-2678-3459","position":5,"is_corresponding":false},{"id":890571,"name":"Stefano Donegà","orcid":"0000-0003-0669-1618","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Rescue of common exon‐skipping mutations in cystic fibrosis with modified U1 snRNAs","abstract":"In cystic fibrosis (CF), the correction of splicing defects represents an interesting therapeutic approach to restore normal CFTR function. In this study, we focused on 10 common mutations/variants 711+3A>G/C, 711+5G>A, TG13T3, TG13T5, TG12T5, 1863C>T, 1898+3A>G, 2789+5G>A, and 3120G>A that induce skipping of the corresponding CFTR exons 5, 10, 13, 16, and 18. To rescue the splicing defects we tested, in a minigene assay, a panel of modified U1 small nuclear RNAs (snRNAs), named Exon Specific U1s (ExSpeU1s), that was engineered to bind to intronic sequences downstream of each defective exon. Using this approach, we show that all 10 splicing mutations analyzed are efficiently corrected by specific ExSpeU1s. Using complementary DNA-splicing competent minigenes, we also show that the ExspeU1-mediated splicing correction at the RNA level recovered the full-length CFTR protein for 1863C>T, 1898+3A>G, 2789+5G>A variants. In addition, detailed mutagenesis experiments performed on exon 13 led us to identify a novel intronic regulatory element involved in the ExSpeU1-mediated splicing rescue. These results provide a common strategy based on modified U1 snRNAs to correct exon skipping in a group of disease-causing CFTR mutations.","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32935393","pmcid":null,"openalex_id":"https://openalex.org/W3085484738","authors":[],"funders":[{"funder_name":"Fondazione per la Ricerca sulla Fibrosi Cistica","grant_id":"FFC #5/2014","title":null}],"total_grants":1,"fwci":0.8632,"citation_percentile":0.7788039,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":3},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"closed","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.24116","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/humu.24116","host_type":"publisher"},{"url":"https://doi.org/10.1002/humu.24116","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32935393","host_type":"repository"}],"fields_of_study":["Cystic Fibrosis Research Advances","Advanced biosensing and bioanalysis techniques","RNA Interference and Gene Delivery","Cystic Fibrosis","Cystic Fibrosis Transmembrane Conductance Regulator","Exons","HeLa Cells","Humans","Introns","Mutation","Nucleic Acid Conformation","RNA Splicing","RNA, Small Nuclear"],"mesh_terms":["Cystic Fibrosis","Exons","HeLa Cells","Humans","Introns","Mutation","Nucleic Acid Conformation","RNA Splicing","RNA, Small Nuclear","Cystic Fibrosis Transmembrane Conductance Regulator","Hela Cells"],"keywords":["Minigene","RNA splicing","Exon","Exon skipping","Biology","Alternative splicing","Genetics","Mutation","Exonic splicing enhancer","Mutagenesis","RNA","Molecular biology","Gene","Personalized Medicine","Theranostics","Rna Therapies"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T23:55:50.859872Z","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":[]}