{"doi":"10.1101/2020.04.03.023606","title":"Programmable RNA Targeting using CasRx in Flies","abstract":"Abstract CRISPR-Cas genome editing technologies have revolutionized the fields of functional genetics and genome engineering, but with the recent discovery and optimization of RNA-targeting Cas ribonucleases, we may soon see a similar revolution in the study of RNA function and transcriptome engineering. However, to date, successful proof-of-principle for Cas ribonuclease RNA targeting in eukaryotic systems has been limited. Only recently has successful modification of RNA expression by a Cas ribonuclease been demonstrated in animal embryos. This previous work, however, did not evaluate endogenous expression of Cas ribonucleases and only focused on Cas ribonuclease function in early developmental stages. A more comprehensive evaluation of this technology is needed to assess its potential impact in the field. Here we report on our efforts to develop a programmable platform for RNA-targeting using a Cas ribonuclease, CasRx, in the model organism Drosophila melanogaster . By genetically encoding CasRx in flies, we demonstrate moderate transcript targeting of known phenotypic genes in addition to unexpected toxicity and lethality. We also report on the off-target effects following on-target transcript cleavage by CasRx. Taken together, our results present the current state and limitations of a genetically encoded programmable RNA-targeting Cas system in Drosophila melanogaster , paving the way for future optimization of the system.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122028,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"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":0.9498,"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":283692,"name":"Dan J. Brogan","orcid":null,"position":1,"is_corresponding":false},{"id":282447,"name":"Ruichen Sun","orcid":"0000-0002-8076-139X","position":2,"is_corresponding":false},{"id":282448,"name":"Ting Yang","orcid":"0000-0001-7201-4231","position":3,"is_corresponding":false},{"id":235423,"name":"Patrick D. Hsu","orcid":"0000-0002-9380-2648","position":4,"is_corresponding":false},{"id":262214,"name":"Omar S. Akbari","orcid":"0000-0002-6853-9884","position":5,"is_corresponding":false},{"id":282255,"name":"Anna Buchman","orcid":"0000-0002-8775-6147","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:46.979435Z","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":[]}