{"doi":"10.17615/627m-7q84","title":"Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides.","abstract":"Antisense 2'-O-methylribooligonucleotides were targeted against specific sequence elements in mutated human beta-globin pre-mRNAs to restore correct splicing of these RNAs in vitro. The following mutations of the beta-globin gene, A-->G at nt 110 of the first intron (beta 110), T-->G at nt 705 and C-->T at nt 654 of the second intron (IVS2(705) and IVS2(654), respectively), which led to aberrant splicing of the corresponding pre-mRNAs, were previously identified as the underlying causes of beta-thalassemia. Aberrant splicing of beta 110 pre-mRNA was efficiently reversed by an oligonucleotide targeted against the branch point sequence in the first intron of the pre-mRNA but not by an oligonucleotide targeted against the aberrant 3' splice site. In both IVS2(705) and IVS2(654) pre-mRNAs, correct splicing was restored by oligonucleotides targeted against the aberrant 5' splice sites created by the mutations in the second intron or against a cryptic 3' splice site located upstream and activated in the mutated background. These experiments represent an approach in which antisense oligonucleotides are used to restore the function of a defective gene and not, as usual, to down-regulate the expression of an undesirable gene.","journal":"UNC Libraries","year":2020,"id":109386,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9419,"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":175169,"name":"Z. Dominski","orcid":null,"position":1,"is_corresponding":false},{"id":175170,"name":"R. Kole","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:12:50.712357Z","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":[]}