{"doi":"10.17615/n80d-bv38","title":"Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs","abstract":"In several forms of β-thalassemia, mutations in the second intron of the β-globin gene create aberrant 5′ splice sites and activate a common cryptic 3′ splice site upstream. As a result, the thalassemic β-globin pre-mRNAs are spliced almost exclusively via the aberrant splice sites leading to a deficiency of correctly spliced β-globin mRNA and, consequently, β-globin. We have designed a series of vectors that express modified U7 snRNAs containing sequences antisense to either the aberrant 5′ or 3′ splice sites in the IVS2–705 thalassemic pre-mRNA. Transient expression of modified U7 snRNAs in a HeLa cell line stably expressing the IVS2–705 β-globin gene restored up to 65% of correct splicing in a sequence-specific and dose-dependent manner. Cell lines that stably coexpressed IVS2–705 pre-mRNA and appropriately modified U7 snRNA exhibited up to 55% of permanent restoration of correct splicing and expression of full-length β-globin protein. This novel approach provides a potential alternative to gene replacement therapies.","journal":"UNC Libraries","year":2020,"id":114655,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"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":539864,"name":"L. Gorman","orcid":null,"position":1,"is_corresponding":false},{"id":539865,"name":"D. Schumperli","orcid":null,"position":2,"is_corresponding":false},{"id":539866,"name":"D. Suter","orcid":null,"position":3,"is_corresponding":false},{"id":539867,"name":"V. Emerick","orcid":null,"position":4,"is_corresponding":false},{"id":175170,"name":"R. Kole","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:33.226937Z","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":[]}