{"doi":"10.1101/2021.05.18.444740","title":"The FusX TALE Base Editor (FusXTBE) for rapid mitochondrial DNA programming of human cells <i>in vitro</i> and zebrafish disease models <i>in vivo</i>","abstract":"Abstract Functional analyses of mitochondria have been hampered by few effective approaches to manipulate mtDNA and a lack of existing animal models. Recently a TALE-derived base editor was shown to induce C-to-T (or G-to-A) sequence changes in mtDNA. We report here the FusX TALE Base Editor (FusXTBE) to facilitate broad-based access to TALE mitochondrial base editing technology. TALE Writer is a de novo in silico design tool to map potential mtDNA base editing sites. FusXTBE was demonstrated to function with comparable activity to the initial base editor in human cells in vitro . Zebrafish embryos were used as a pioneering in vivo test system, with FusXTBE inducing 90+% editing efficiency in mtDNA loci, the first example of majority mtDNA heteroplasmy induction in any system. Gene editing specificity as precise as a single nucleotide was observed in vivo for a protein-coding gene. Non-destructive genotyping enables single animal mtDNA analyses for downstream biological functional genomics applications. FusXTBE is a new gene editing toolkit for exploring important questions in mitochondrial biology and genetics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215894,"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":0.9484,"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":785780,"name":"Bibekananda Kar","orcid":"0000-0001-8794-1513","position":1,"is_corresponding":false},{"id":785779,"name":"Santiago Restrepo-Castillo","orcid":"0000-0001-7881-1813","position":2,"is_corresponding":false},{"id":811219,"name":"Shannon R. Holmberg","orcid":"0000-0003-2442-0029","position":3,"is_corresponding":false},{"id":435571,"name":"Benjamin L. Kendall","orcid":"0000-0002-7002-7474","position":4,"is_corresponding":false},{"id":811220,"name":"Ryan P. Cotter","orcid":"0000-0002-7798-7443","position":5,"is_corresponding":false},{"id":811221,"name":"Zachary WareJoncas","orcid":"0000-0003-0714-8641","position":6,"is_corresponding":false},{"id":254327,"name":"Karl J. Clark","orcid":"0000-0002-9637-0967","position":7,"is_corresponding":false},{"id":254326,"name":"Stephen C. Ekker","orcid":"0000-0003-0726-4212","position":8,"is_corresponding":false},{"id":413662,"name":"Ankit Sabharwal","orcid":"0000-0003-4355-0355","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-18T23:53:00.192353Z","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":[]}