{"doi":"10.1101/2020.07.13.200998","title":"Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing","abstract":"Genome editing has promising therapeutic potential for genetic diseases and cancer (1, 2). However, the most practicable current approaches rely on the generation of DNA double-strand breaks (DSBs), which can give rise to a poorly characterized spectrum of structural chromosomal abnormalities. Here, we show that a catastrophic mutational process called chromothripsis is a previously unappreciated consequence of CRISPR-Cas9-mediated DSBs. Chromothripsis is extensive chromosome rearrangement restricted to one or a few chromosomes that can cause human congenital disease and cancer (3–6). Using model cell systems and a genome editing protocol similar to ones in clinical trials (7) ( NCT03655678 , NCT03745287 ) we show that CRISPR-Cas9-mediated DNA breaks generate abnormal nuclear structures—micronuclei and chromosome bridges—that trigger chromothripsis. Chromothripsis is an on-target toxicity that may be minimized by cell manipulation protocols or screening but cannot be completely avoided in many genome editing applications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118541,"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":63,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"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":550880,"name":"Stamatis Papathanasiou","orcid":"0000-0001-6969-044X","position":1,"is_corresponding":false},{"id":550881,"name":"Phillip A. Doerfler","orcid":"0000-0001-7566-9073","position":2,"is_corresponding":false},{"id":227874,"name":"Logan J. Blaine","orcid":"0000-0003-0937-9216","position":3,"is_corresponding":false},{"id":550882,"name":"Yu Yao","orcid":"0000-0001-9286-4014","position":4,"is_corresponding":false},{"id":14472,"name":"Cheng‐Zhong Zhang","orcid":"0000-0001-8825-7158","position":5,"is_corresponding":false},{"id":90394,"name":"Mitchell J. Weiss","orcid":"0000-0003-2460-3036","position":6,"is_corresponding":false},{"id":108498,"name":"David Pellman","orcid":"0000-0001-5306-8031","position":7,"is_corresponding":false},{"id":19049,"name":"Mitchell L. Leibowitz","orcid":"0000-0003-1874-5441","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T23:13:58.531532Z","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":[]}