{"doi":"10.1073/pnas.0812502106","title":"Synthesis of programmable integrases","abstract":"<jats:p>Accurate modification of the 3 billion-base-pair human genome requires tools with exceptional sequence specificity. Here, we describe a general strategy for the design of enzymes that target a single site within the genome. We generated chimeric zinc finger recombinases with cooperative DNA-binding and catalytic specificities that integrate transgenes with &gt;98% accuracy into the human genome. These modular recombinases can be reprogrammed: New combinations of zinc finger domains and serine recombinase catalytic domains generate novel enzymes with distinct substrate sequence specificities. Because of their accuracy and versatility, the recombinases/integrases reported in this work are suitable for a wide variety of applications in biological research, medicine, and biotechnology where accurate delivery of DNA is desired.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2009,"id":615590,"datarank":0.6798899239729885,"base_score":4.532599493153256,"endowment":4.532599493153256,"self_citation_contribution":0.6798899239729885,"citation_network_contribution":0.0,"self_endowment_contribution":0.6798899239729885,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":92,"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":29946,"name":"Charles A. Gersbach","orcid":"0000-0003-1478-4013","position":1,"is_corresponding":false},{"id":127613,"name":"Carlos F. Barbas","orcid":null,"position":2,"is_corresponding":false},{"id":1211662,"name":"Russell M. Gordley","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Synthesis of programmable integrases","abstract":"<jats:p>Accurate modification of the 3 billion-base-pair human genome requires tools with exceptional sequence specificity. Here, we describe a general strategy for the design of enzymes that target a single site within the genome. We generated chimeric zinc finger recombinases with cooperative DNA-binding and catalytic specificities that integrate transgenes with &gt;98% accuracy into the human genome. These modular recombinases can be reprogrammed: New combinations of zinc finger domains and serine recombinase catalytic domains generate novel enzymes with distinct substrate sequence specificities. Because of their accuracy and versatility, the recombinases/integrases reported in this work are suitable for a wide variety of applications in biological research, medicine, and biotechnology where accurate delivery of DNA is desired.</jats:p>","is_dataset_classified":null,"base_score":4.532599493153256,"endowment":4.532599493153256,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19282480","pmcid":"PMC2654808","openalex_id":"https://openalex.org/W2070055731","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R21CA126664","title":null},{"funder_name":"NCI NIH HHS","grant_id":"F32 CA125910","title":null}],"total_grants":2,"fwci":5.2917,"citation_percentile":0.96571238,"influential_citations":0,"citation_trend":[{"year":2012,"count":12},{"year":2013,"count":8},{"year":2014,"count":9},{"year":2015,"count":5},{"year":2016,"count":4},{"year":2017,"count":4},{"year":2018,"count":7},{"year":2019,"count":3},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2024,"count":3},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2654808","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2654808","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0812502106","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0812502106","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19282480","host_type":"repository"}],"fields_of_study":["CRISPR and Genetic Engineering","Virus-based gene therapy research","RNA Interference and Gene Delivery"],"mesh_terms":["Binding Sites","DNA-Binding Proteins","Humans","Recombinant Fusion Proteins","Substrate Specificity","Protein Engineering","Genome, Human","Zinc Fingers","Gene Targeting","Transgenes","Integrases","Catalytic Domain","Recombinases","Gene Knock-In Techniques"],"keywords":["Recombinase","Integrases","Computational biology","Zinc finger nuclease","Tn3 transposon","DNA","Genome","Genome editing","Biology","Zinc finger","Synthetic biology","Human genome","Genetics","Integrase","Transposable element","Gene","Recombination","Transcription factor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T20:29:30.024627Z","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":[]}