{"doi":"10.1093/nar/gky804","title":"Highly efficient genome editing via CRISPR–Cas9 in human pluripotent stem cells is achieved by transient BCL-XL overexpression","abstract":null,"journal":"Nucleic Acids Research","year":2018,"id":654997,"datarank":0.7206031567099886,"base_score":4.804021044733257,"endowment":4.804021044733257,"self_citation_contribution":0.7206031567099886,"citation_network_contribution":0.0,"self_endowment_contribution":0.7206031567099886,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":121,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1709592,"name":"Guo-Hua Li","orcid":null,"position":1,"is_corresponding":false},{"id":514095,"name":"Juan Fu","orcid":null,"position":2,"is_corresponding":false},{"id":1709595,"name":"Ya-Wen Fu","orcid":"0000-0002-7752-2005","position":3,"is_corresponding":false},{"id":1128466,"name":"Lu Zhang","orcid":"0000-0001-8358-6112","position":4,"is_corresponding":false},{"id":271305,"name":"Wanqiu Chen","orcid":"0000-0003-3706-7834","position":5,"is_corresponding":false},{"id":1709597,"name":"Cameron Arakaki","orcid":null,"position":6,"is_corresponding":false},{"id":1709598,"name":"Jian-Ping Zhang","orcid":null,"position":7,"is_corresponding":false},{"id":1111928,"name":"Wei Wen","orcid":"0000-0002-5485-0372","position":8,"is_corresponding":false},{"id":493512,"name":"Mei Zhao","orcid":"0000-0003-4204-9235","position":9,"is_corresponding":false},{"id":1709599,"name":"Weisheng V Chen","orcid":null,"position":10,"is_corresponding":false},{"id":1709600,"name":"Gary D Botimer","orcid":null,"position":11,"is_corresponding":false},{"id":1709601,"name":"David Baylink","orcid":null,"position":12,"is_corresponding":false},{"id":1709602,"name":"Leslie Aranda","orcid":null,"position":13,"is_corresponding":false},{"id":271309,"name":"Hannah Choi","orcid":"0000-0002-8192-1121","position":14,"is_corresponding":false},{"id":1709603,"name":"Rachel Bechar","orcid":null,"position":15,"is_corresponding":false},{"id":330683,"name":"Prue Talbot","orcid":"0000-0001-8833-0845","position":16,"is_corresponding":false},{"id":1709604,"name":"Chang-Kai Sun","orcid":null,"position":17,"is_corresponding":false},{"id":51585,"name":"Tao Cheng","orcid":"0000-0002-5925-2769","position":18,"is_corresponding":false},{"id":1507949,"name":"Xiao-Bing Zhang","orcid":null,"position":19,"is_corresponding":false},{"id":1709590,"name":"Xiao-Lan Li","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Highly efficient genome editing via CRISPR–Cas9 in human pluripotent stem cells is achieved by transient BCL-XL overexpression","abstract":"Genome editing of human induced pluripotent stem cells (iPSCs) is instrumental for functional genomics, disease modeling, and regenerative medicine. However, low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockin (KI) or knockout (KO) iPSC lines, which is largely due to massive cell death after electroporation with editing plasmids. Here, we report that the transient delivery of BCL-XL increases iPSC survival by ∼10-fold after plasmid transfection, leading to a 20- to 100-fold increase in homology-directed repair (HDR) KI efficiency and a 5-fold increase in non-homologous end joining (NHEJ) KO efficiency. Treatment with a BCL inhibitor ABT-263 further improves HDR efficiency by 70% and KO efficiency by 40%. The increased genome editing efficiency is attributed to higher expressions of Cas9 and sgRNA in surviving cells after electroporation. HDR or NHEJ efficiency reaches 95% with dual editing followed by selection of cells with HDR insertion of a selective gene. Moreover, KO efficiency of 100% can be achieved in a bulk population of cells with biallelic HDR KO followed by double selection, abrogating the necessity for single cell cloning. Taken together, these simple yet highly efficient editing strategies provide useful tools for applications ranging from manipulating human iPSC genomes to creating gene-modified animal models.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30239926","pmcid":"PMC6212847","openalex_id":null,"authors":[],"funders":[{"funder_name":"Ministry of Science and Technology of China","grant_id":"2015CB964902","title":null},{"funder_name":"Ministry of Science and Technology of China","grant_id":"2015CB964400","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81700183","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81770198","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81500148","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81570164","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81421002","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81870149","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"8170018","title":null},{"funder_name":"Chinese Academy of Medical Sciences","grant_id":"2017-I2M-B&R-04","title":null},{"funder_name":"Chinese Academy of Medical Sciences","grant_id":"2017-I2M-1–015","title":null},{"funder_name":"Chinese Academy of Medical Sciences","grant_id":"2016-I2M-1–017","title":null},{"funder_name":"Chinese Academy of Medical Sciences","grant_id":"2018PT31004","title":null},{"funder_name":"Chinese Academy of Medical Sciences","grant_id":"2016ZX310184-3","title":null},{"funder_name":"CAMS Key Laboratory of Gene Therapy for Blood Diseases","grant_id":"2017PT31047","title":null},{"funder_name":"CAMS Key Laboratory of Gene Therapy for Blood Diseases","grant_id":"2018PT31038","title":null},{"funder_name":"Fundamental Research Funds for Central Universities","grant_id":"DUT18ZD301","title":null},{"funder_name":"State Key Laboratory of Bioelectronics, Southeast University","grant_id":"ZX20180025","title":null},{"funder_name":"Loma Linda University","grant_id":"681171-2967","title":null},{"funder_name":"Chinese Academy of Medical Sciences","grant_id":"2017-I2M-B&R-04","title":null}],"total_grants":20,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/nar/article-pdf/46/19/10195/26333851/gky804.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/nar/article-pdf/46/19/10195/26333851/gky804.pdf","host_type":"publisher"},{"url":"https://escholarship.org/uc/item/08w3p0h9","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC6212847","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6212847","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6212847","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6212847?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Cells, Cultured","Jurkat Cells","K562 Cells","Animals","Humans","Mice","Transfection","Up-Regulation","Genome, Human","bcl-X Protein","Induced Pluripotent Stem Cells","HEK293 Cells","CRISPR-Cas Systems","Gene Editing"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T09:14:47.112724Z","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":[]}