{"id":"https://openalex.org/W4200210218","doi":"https://doi.org/10.1093/nar/gkab1214","title":"Rational design and construction of multi-copy biomanufacturing islands in mammalian cells","display_name":"Rational design and construction of multi-copy biomanufacturing islands in mammalian cells","publication_year":2021,"publication_date":"2021-11-26","ids":{"openalex":"https://openalex.org/W4200210218","doi":"https://doi.org/10.1093/nar/gkab1214","pmid":"https://pubmed.ncbi.nlm.nih.gov/34893882","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/8754653"},"language":"en","primary_location":{"id":"doi:10.1093/nar/gkab1214","doi":"https://doi.org/10.1093/nar/gkab1214","is_oa":true,"landing_page_url":"https://doi.org/10.1093/nar/gkab1214","pdf_url":"https://academic.oup.com/nar/article-pdf/50/1/561/42149167/gkab1214.pdf","source":{"id":"https://openalex.org/S134668137","display_name":"Nucleic Acids Research","issn_l":"0305-1048","issn":["0305-1048","1362-4954","1362-4962"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nucleic Acids Research","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","datacite","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://academic.oup.com/nar/article-pdf/50/1/561/42149167/gkab1214.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5048528265","display_name":"Raffaele Altamura","orcid":"https://orcid.org/0000-0003-3244-3247","observed_orcids":["https://orcid.org/0000-0003-3244-3247"]},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Raffaele Altamura","raw_affiliation_strings":["Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland"],"raw_orcid":"https://orcid.org/0000-0003-3244-3247","affiliations":[{"raw_affiliation_string":"Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064483842","display_name":"Jiten Doshi","orcid":"https://orcid.org/0009-0002-2887-1943","observed_orcids":["https://orcid.org/0009-0002-2887-1943"]},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Jiten Doshi","raw_affiliation_strings":["Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5072659013","display_name":"Yaakov Benenson","orcid":"https://orcid.org/0000-0003-1880-6507","observed_orcids":["https://orcid.org/0000-0003-1880-6507"]},"institutions":[{"id":"https://openalex.org/I35440088","display_name":"ETH Zurich","ror":"https://ror.org/05a28rw58","country_code":"CH","type":"education","lineage":["https://openalex.org/I2799323385","https://openalex.org/I35440088"]}],"countries":["CH"],"is_corresponding":true,"raw_author_name":"Yaakov Benenson","raw_affiliation_strings":["Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland"],"raw_orcid":"https://orcid.org/0000-0003-1880-6507","affiliations":[{"raw_affiliation_string":"Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland","institution_ids":["https://openalex.org/I35440088"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5072659013"],"corresponding_institution_ids":["https://openalex.org/I35440088"],"apc_list":{"value":3800,"currency":"USD","value_usd":3800},"apc_paid":{"value":3800,"currency":"USD","value_usd":3800},"fwci":0.3923,"has_fulltext":true,"cited_by_count":10,"citation_normalized_percentile":{"value":0.52989561,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"50","issue":"1","first_page":"561","last_page":"578"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.9883000254631042,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.9883000254631042,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10613","display_name":"Virus-based gene therapy research","score":0.004399999976158142,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12929","display_name":"Animal Genetics and Reproduction","score":0.002099999925121665,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/transgene-integration","display_name":"transgene integration","score":0.8019999861717224},{"id":"https://openalex.org/keywords/sequence-optimization","display_name":"sequence optimization","score":0.6589999794960022},{"id":"https://openalex.org/keywords/cho-cells","display_name":"CHO cells","score":0.39500001072883606},{"id":"https://openalex.org/keywords/recombinant-protein-expression","display_name":"recombinant protein expression","score":0.7940000295639038},{"id":"https://openalex.org/keywords/biopharmaceutical-manufacturing","display_name":"biopharmaceutical manufacturing","score":0.6539999842643738},{"id":"https://openalex.org/keywords/cell-line-development","display_name":"cell line development","score":0.7760000228881836},{"id":"https://openalex.org/keywords/chromosomal-integration","display_name":"chromosomal integration","score":0.5870000123977661},{"id":"https://openalex.org/keywords/transient-transfection","display_name":"transient transfection","score":0.640999972820282}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8861743807792664},{"id":"https://openalex.org/C2775893736","wikidata":"https://www.wikidata.org/wiki/Q25324110","display_name":"Biomanufacturing","level":2,"score":0.7739164233207703},{"id":"https://openalex.org/C102230213","wikidata":"https://www.wikidata.org/wiki/Q430117","display_name":"Transgene","level":3,"score":0.6869560480117798},{"id":"https://openalex.org/C2781047461","wikidata":"https://www.wikidata.org/wiki/Q679692","display_name":"Biopharmaceutical","level":2,"score":0.5668853521347046},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5600590109825134},{"id":"https://openalex.org/C191908910","wikidata":"https://www.wikidata.org/wiki/Q862838","display_name":"Synthetic biology","level":2,"score":0.5203575491905212},{"id":"https://openalex.org/C161733203","wikidata":"https://www.wikidata.org/wiki/Q911828","display_name":"Reporter gene","level":4,"score":0.50861656665802},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5011272430419922},{"id":"https://openalex.org/C91779695","wikidata":"https://www.wikidata.org/wiki/Q3780824","display_name":"Coding region","level":3,"score":0.4436625838279724},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.388049453496933},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.26100248098373413}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003412","descriptor_name":"Cricetulus","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005822","descriptor_name":"Genetic Vectors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011994","descriptor_name":"Recombinant Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D016466","descriptor_name":"CHO Cells","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018390","descriptor_name":"Gene Targeting","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019076","descriptor_name":"Transgenes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":5,"locations":[{"id":"doi:10.1093/nar/gkab1214","doi":"https://doi.org/10.1093/nar/gkab1214","is_oa":true,"landing_page_url":"https://doi.org/10.1093/nar/gkab1214","pdf_url":"https://academic.oup.com/nar/article-pdf/50/1/561/42149167/gkab1214.pdf","source":{"id":"https://openalex.org/S134668137","display_name":"Nucleic Acids Research","issn_l":"0305-1048","issn":["0305-1048","1362-4954","1362-4962"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nucleic Acids Research","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8754653","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8754653","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nucleic Acids Res","raw_type":"Text"},{"id":"pmid:34893882","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34893882","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nucleic acids research","raw_type":"Journal Article"},{"id":"pmh:oai:www.research-collection.ethz.ch:20.500.11850/528625","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/20.500.11850/528625","pdf_url":null,"source":{"id":"https://openalex.org/S4306402302","display_name":"Repository for Publications and Research Data (ETH Zurich)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I35440088","host_organization_name":"ETH Zurich","host_organization_lineage":["https://openalex.org/I35440088"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nucleic Acids Research, 50 (1)","raw_type":"info:eu-repo/semantics/article"},{"id":"doi:10.3929/ethz-b-000528625","doi":"https://doi.org/10.3929/ethz-b-000528625","is_oa":true,"landing_page_url":"https://doi.org/10.3929/ethz-b-000528625","pdf_url":null,"source":{"id":"https://openalex.org/S7407051236","display_name":"ETH Z\u00fcrich Research Collection","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"article-journal"}],"best_oa_location":{"id":"doi:10.1093/nar/gkab1214","doi":"https://doi.org/10.1093/nar/gkab1214","is_oa":true,"landing_page_url":"https://doi.org/10.1093/nar/gkab1214","pdf_url":"https://academic.oup.com/nar/article-pdf/50/1/561/42149167/gkab1214.pdf","source":{"id":"https://openalex.org/S134668137","display_name":"Nucleic Acids Research","issn_l":"0305-1048","issn":["0305-1048","1362-4954","1362-4962"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nucleic Acids Research","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320320924","display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","ror":"https://ror.org/00yjd3n13"},{"id":"https://openalex.org/F4320321652","display_name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","ror":"https://ror.org/05a28rw58"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4200210218.pdf","grobid_xml":"https://content.openalex.org/works/W4200210218.grobid-xml"},"referenced_works_count":68,"referenced_works":["https://openalex.org/W1488701566","https://openalex.org/W1495020242","https://openalex.org/W1574936994","https://openalex.org/W1758061342","https://openalex.org/W1798017247","https://openalex.org/W1938349683","https://openalex.org/W1966212700","https://openalex.org/W1968389447","https://openalex.org/W1968741040","https://openalex.org/W1975777043","https://openalex.org/W1982609556","https://openalex.org/W2002635086","https://openalex.org/W2004635090","https://openalex.org/W2005343613","https://openalex.org/W2018590530","https://openalex.org/W2033433083","https://openalex.org/W2034979835","https://openalex.org/W2037174767","https://openalex.org/W2043911972","https://openalex.org/W2049627734","https://openalex.org/W2049974202","https://openalex.org/W2051242197","https://openalex.org/W2059464705","https://openalex.org/W2062736124","https://openalex.org/W2074715180","https://openalex.org/W2078988344","https://openalex.org/W2083276287","https://openalex.org/W2083796374","https://openalex.org/W2085754069","https://openalex.org/W2086561953","https://openalex.org/W2087439897","https://openalex.org/W2090037733","https://openalex.org/W2099687964","https://openalex.org/W2100209798","https://openalex.org/W2100508150","https://openalex.org/W2102228626","https://openalex.org/W2118540273","https://openalex.org/W2119855539","https://openalex.org/W2139180337","https://openalex.org/W2145301070","https://openalex.org/W2145668963","https://openalex.org/W2151102421","https://openalex.org/W2152052780","https://openalex.org/W2154031143","https://openalex.org/W2154853638","https://openalex.org/W2157913328","https://openalex.org/W2166709050","https://openalex.org/W2172134808","https://openalex.org/W2186082751","https://openalex.org/W2196385701","https://openalex.org/W2278619766","https://openalex.org/W2586988241","https://openalex.org/W2613991881","https://openalex.org/W2802915411","https://openalex.org/W2803643875","https://openalex.org/W2806593488","https://openalex.org/W2887092751","https://openalex.org/W2888734161","https://openalex.org/W2895888195","https://openalex.org/W2917928050","https://openalex.org/W2945580095","https://openalex.org/W2998372626","https://openalex.org/W3000778706","https://openalex.org/W3041065315","https://openalex.org/W3048652949","https://openalex.org/W3081088497","https://openalex.org/W4244544159","https://openalex.org/W6641828010"],"related_works":["https://openalex.org/W2138781976","https://openalex.org/W3081088497","https://openalex.org/W6992239694","https://openalex.org/W2802915411","https://openalex.org/W4409776783","https://openalex.org/W2962821611","https://openalex.org/W3015359834","https://openalex.org/W4392455623","https://openalex.org/W2883052546","https://openalex.org/W4383186073"],"abstract_inverted_index":{"Cell":[0],"line":[1,188],"development":[2],"is":[3,90],"a":[4,11,62,109,131,135,163,176,185],"critical":[5],"step":[6],"in":[7,28,35,140,184],"the":[8,66,91,94,98,149,154,172],"establishment":[9],"of":[10,73,79,97,124,174],"biopharmaceutical":[12],"manufacturing":[13],"process.":[14],"Current":[15],"protocols":[16],"rely":[17],"on":[18,134,153],"random":[19],"transgene":[20,29,48],"integration":[21,30,52,72],"and":[22,51,70,114,118,130,196],"amplification.":[23],"Due":[24],"to":[25,81,87,126,171],"considerable":[26],"variability":[27],"profiles,":[31],"this":[32,58,88],"workflow":[33,111],"results":[34],"laborious":[36],"screening":[37,192],"campaigns":[38],"before":[39],"stable":[40],"producers":[41],"can":[42],"be":[43],"identified.":[44],"Alternative":[45],"approaches":[46],"for":[47,65,112],"dosage":[49],"increase":[50],"are":[53],"therefore":[54],"highly":[55],"desirable.":[56],"In":[57],"study,":[59],"we":[60,157],"present":[61],"novel":[63],"strategy":[64,89],"rapid":[67],"design,":[68],"construction,":[69],"genomic":[71,165],"engineered":[74],"multiple-copy":[75],"gene":[76,83,100,128,150],"constructs":[77],"consisting":[78],"up":[80,125],"10":[82],"expression":[84,146],"cassettes.":[85],"Key":[86],"diversification,":[92],"at":[93],"sequence":[95,116],"level,":[96],"individual":[99],"cassettes":[101,161],"without":[102],"altering":[103],"their":[104],"protein":[105,145,181],"products.":[106],"We":[107],"show":[108],"computational":[110],"coding":[113],"regulatory":[115],"diversification":[117],"optimization":[119],"followed":[120],"by":[121],"experimental":[122],"assembly":[123],"nine":[127],"copies":[129],"sentinel":[132],"reporter":[133],"contiguous":[136],"scaffold.":[137,155],"Transient":[138],"transfections":[139],"CHO":[141],"cells":[142],"indicates":[143],"that":[144],"increases":[147],"with":[148,189],"copy":[151],"number":[152],"Further,":[156],"stably":[158],"integrate":[159],"these":[160],"into":[162],"pre-validated":[164],"locus.":[166],"Altogether,":[167],"our":[168],"findings":[169],"point":[170],"feasibility":[173],"engineering":[175],"fully":[177],"mapped":[178],"multi-copy":[179],"recombinant":[180],"'production":[182],"island'":[183],"mammalian":[186],"cell":[187],"greatly":[190],"reduced":[191],"effort,":[193],"improved":[194],"stability,":[195],"predictable":[197],"product":[198],"titers.":[199]},"counts_by_year":[{"year":2025,"cited_by_count":5},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2021-12-31T00:00:00"}