{"doi":"10.1038/s41467-021-22009-2","title":"CRISPR-Cas9 cytidine and adenosine base editing of splice-sites mediates highly-efficient disruption of proteins in primary and immortalized cells","abstract":"CRISPR-Cas9 cytidine and adenosine base editors (CBEs and ABEs) can disrupt genes without introducing double-stranded breaks by inactivating splice sites (BE-splice) or by introducing premature stop (pmSTOP) codons. However, no in-depth comparison of these methods or a modular tool for designing BE-splice sgRNAs exists. To address these needs, we develop SpliceR ( http://z.umn.edu/spliceR ) to design and rank BE-splice sgRNAs for any Ensembl annotated genome, and compared disruption approaches in T cells using a screen against the TCR-CD3 MHC Class I immune synapse. Among the targeted genes, we find that targeting splice-donors is the most reliable disruption method, followed by targeting splice-acceptors, and introducing pmSTOPs. Further, the CBE BE4 is more effective for disruption than the ABE ABE7.10, however this disparity is eliminated by employing ABE8e. Collectively, we demonstrate a robust method for gene disruption, accompanied by a modular design tool that is of use to basic and translational researchers alike.","journal":"Nature Communications","year":2021,"id":148909,"datarank":0.7168685239667295,"base_score":4.77912349311153,"endowment":4.77912349311153,"self_citation_contribution":0.7168685239667295,"citation_network_contribution":0.0,"self_endowment_contribution":0.7168685239667295,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":118,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":555934,"name":"Walker S. Lahr","orcid":"0000-0002-3288-3843","position":1,"is_corresponding":false},{"id":633217,"name":"Cara-lin Lonetree","orcid":"0000-0002-2760-8572","position":2,"is_corresponding":false},{"id":362552,"name":"Branden A. Smeester","orcid":null,"position":3,"is_corresponding":false},{"id":633911,"name":"Xiaohong Qiu","orcid":null,"position":4,"is_corresponding":false},{"id":417672,"name":"Nicholas J. Slipek","orcid":"0000-0003-2664-6507","position":5,"is_corresponding":false},{"id":633218,"name":"Patricia Claudio-Vázquez","orcid":"0000-0003-2754-4895","position":6,"is_corresponding":false},{"id":633219,"name":"Samuel P. Pitzen","orcid":"0000-0001-6556-0461","position":7,"is_corresponding":false},{"id":417675,"name":"Emily J. Pomeroy","orcid":"0000-0001-7690-3570","position":8,"is_corresponding":false},{"id":633912,"name":"Madison J. Vignes","orcid":null,"position":9,"is_corresponding":false},{"id":633220,"name":"Samantha C. Lee","orcid":"0000-0002-2794-2706","position":10,"is_corresponding":false},{"id":633221,"name":"Samuel P. Bingea","orcid":"0000-0001-7479-8180","position":11,"is_corresponding":false},{"id":633913,"name":"Aneesha A. Andrew","orcid":null,"position":12,"is_corresponding":false},{"id":254328,"name":"Beau R. Webber","orcid":"0000-0002-3950-8747","position":13,"is_corresponding":false},{"id":254329,"name":"Branden S. Moriarity","orcid":"0000-0002-3031-3767","position":14,"is_corresponding":false},{"id":633216,"name":"Mitchell G. Kluesner","orcid":"0000-0001-5828-9204","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:46.224799Z","pmid":"33893286","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":[]}