{"id":"https://openalex.org/W4407410347","doi":"https://doi.org/10.7554/elife.104320","title":"Synthetic gene circuits that selectively target RAS-driven cancers","display_name":"Synthetic gene circuits that selectively target RAS-driven cancers","publication_year":2025,"publication_date":"2025-02-12","ids":{"openalex":"https://openalex.org/W4407410347","doi":"https://doi.org/10.7554/elife.104320","pmid":"https://pubmed.ncbi.nlm.nih.gov/41733988","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/12931925"},"language":"en","primary_location":{"id":"doi:10.7554/elife.104320","doi":"https://doi.org/10.7554/elife.104320","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.104320","pdf_url":"https://elifesciences.org/reviewed-preprints/104320.pdf","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},"volume":null,"type":"preprint","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://elifesciences.org/reviewed-preprints/104320.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5114592205","display_name":"Gabriel Valentin Senn","orcid":"https://orcid.org/0009-0002-7123-2899","observed_orcids":["https://orcid.org/0009-0002-7123-2899"]},"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":"Gabriel Valentin Senn","raw_affiliation_strings":["Department of Biosystems Science and Engineering, ETH Zurich"],"raw_orcid":"https://orcid.org/0009-0002-7123-2899","affiliations":[{"raw_affiliation_string":"Department of Biosystems Science and Engineering, ETH Zurich","institution_ids":["https://openalex.org/I35440088"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063725266","display_name":"Leon Nissen","orcid":"https://orcid.org/0009-0009-3272-834X","observed_orcids":["https://orcid.org/0009-0009-3272-834X"]},"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":"Leon Nissen","raw_affiliation_strings":["Department of Biosystems Science and Engineering, ETH Zurich"],"raw_orcid":"https://orcid.org/0009-0009-3272-834X","affiliations":[{"raw_affiliation_string":"Department of Biosystems Science and Engineering, ETH Zurich","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"],"raw_orcid":"https://orcid.org/0000-0003-1880-6507","affiliations":[{"raw_affiliation_string":"Department of Biosystems Science and Engineering, ETH Zurich","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":3000,"currency":"USD","value_usd":2500},"apc_paid":{"value":3000,"currency":"USD","value_usd":2500},"fwci":null,"has_fulltext":true,"cited_by_count":2,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"14","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10621","display_name":"Gene Regulatory Network Analysis","score":0.9663000106811523,"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/T10621","display_name":"Gene Regulatory Network Analysis","score":0.9663000106811523,"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/T10878","display_name":"CRISPR and Genetic Engineering","score":0.006800000090152025,"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/T12996","display_name":"Cancer Research and Treatments","score":0.006399999838322401,"subfield":{"id":"https://openalex.org/subfields/1305","display_name":"Biotechnology"},"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/synthetic-gene-circuits","display_name":"synthetic gene circuits","score":0.9909999966621399},{"id":"https://openalex.org/keywords/ras-mutations","display_name":"RAS mutations","score":0.8100000023841858},{"id":"https://openalex.org/keywords/ras-driven-cancers","display_name":"RAS-driven cancers","score":0.9129999876022339},{"id":"https://openalex.org/keywords/circuit-design","display_name":"circuit design","score":0.45100000500679016},{"id":"https://openalex.org/keywords/circuit-modeling","display_name":"circuit modeling","score":0.6370000243186951},{"id":"https://openalex.org/keywords/cancer-therapy","display_name":"cancer therapy","score":0.35899999737739563}],"concepts":[{"id":"https://openalex.org/C134146338","wikidata":"https://www.wikidata.org/wiki/Q1815901","display_name":"Electronic circuit","level":2,"score":0.5233444571495056},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4444350302219391},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.4390893578529358},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3988088071346283},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3963939845561981},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.37578117847442627},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2900102734565735},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.14545050263404846},{"id":"https://openalex.org/C119599485","wikidata":"https://www.wikidata.org/wiki/Q43035","display_name":"Electrical engineering","level":1,"score":0.11127287149429321}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005813","descriptor_name":"Genes, Synthetic","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":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000628","qualifier_name":"therapy","is_major_topic":true},{"descriptor_ui":"D018631","descriptor_name":"ras Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D018631","descriptor_name":"ras Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053263","descriptor_name":"Gene Regulatory Networks","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D058615","descriptor_name":"Synthetic Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.7554/elife.104320","doi":"https://doi.org/10.7554/elife.104320","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.104320","pdf_url":"https://elifesciences.org/reviewed-preprints/104320.pdf","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},{"id":"pmid:41733988","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41733988","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":"eLife","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:12931925","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12931925/","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","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:8725100f1e2c471ca99914a1755465b3","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/8725100f1e2c471ca99914a1755465b3","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","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":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"eLife, Vol 14 (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.7554/elife.104320","doi":"https://doi.org/10.7554/elife.104320","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.104320","pdf_url":"https://elifesciences.org/reviewed-preprints/104320.pdf","source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"eLife","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.6240000128746033}],"study_designs":[],"awards":[],"funders":[{"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/W4407410347.pdf","grobid_xml":"https://content.openalex.org/works/W4407410347.grobid-xml"},"referenced_works_count":68,"referenced_works":["https://openalex.org/W203023708","https://openalex.org/W1505436131","https://openalex.org/W1977244261","https://openalex.org/W1993990980","https://openalex.org/W2014473902","https://openalex.org/W2042352676","https://openalex.org/W2052591083","https://openalex.org/W2053133779","https://openalex.org/W2054946171","https://openalex.org/W2061425021","https://openalex.org/W2068177524","https://openalex.org/W2068571186","https://openalex.org/W2072319964","https://openalex.org/W2082398508","https://openalex.org/W2102137830","https://openalex.org/W2105826358","https://openalex.org/W2134128731","https://openalex.org/W2137693585","https://openalex.org/W2143935782","https://openalex.org/W2145003445","https://openalex.org/W2145678539","https://openalex.org/W2159628790","https://openalex.org/W2163638464","https://openalex.org/W2164296283","https://openalex.org/W2246817658","https://openalex.org/W2322386893","https://openalex.org/W2335761521","https://openalex.org/W2510602644","https://openalex.org/W2557660307","https://openalex.org/W2559900897","https://openalex.org/W2735652142","https://openalex.org/W2765237233","https://openalex.org/W2771729549","https://openalex.org/W2776289096","https://openalex.org/W2781620758","https://openalex.org/W2782869690","https://openalex.org/W2789289999","https://openalex.org/W2805978167","https://openalex.org/W2806304252","https://openalex.org/W2810238193","https://openalex.org/W2919790554","https://openalex.org/W2978897986","https://openalex.org/W2980948969","https://openalex.org/W2987521332","https://openalex.org/W2994825712","https://openalex.org/W3005430313","https://openalex.org/W3013279701","https://openalex.org/W3013377779","https://openalex.org/W3025847794","https://openalex.org/W3036759197","https://openalex.org/W3037152991","https://openalex.org/W3045897752","https://openalex.org/W3095302783","https://openalex.org/W3112755147","https://openalex.org/W3117806362","https://openalex.org/W3131852822","https://openalex.org/W3164618546","https://openalex.org/W3173843039","https://openalex.org/W3176880957","https://openalex.org/W3177828909","https://openalex.org/W4200299002","https://openalex.org/W4221109056","https://openalex.org/W4249558460","https://openalex.org/W4295037692","https://openalex.org/W4317745734","https://openalex.org/W4382810708","https://openalex.org/W4385827573","https://openalex.org/W6747540930"],"related_works":["https://openalex.org/W6966346093","https://openalex.org/W4413818775","https://openalex.org/W6921435162","https://openalex.org/W4307512593","https://openalex.org/W2126702649","https://openalex.org/W2275848754","https://openalex.org/W1893870576","https://openalex.org/W2942604302","https://openalex.org/W2471368858","https://openalex.org/W2747654131"],"abstract_inverted_index":{"mutation":[0],"and":[1,14,86,107,127],"prone":[2],"to":[3,22,41,67,104,137],"resistance.":[4],"Synthetic":[5],"gene":[6,62,163],"circuits":[7,35,103,118,164],"offer":[8],"a":[9,53,82,141,166],"promising":[10],"alternative":[11],"by":[12,119,134],"sensing":[13],"integrating":[15],"cancer-specific":[16],"biomolecular":[17],"inputs,":[18],"including":[19],"mutated":[20,75,154],"RAS,":[21],"selectively":[23],"express":[24,68],"therapeutic":[25,132,168],"proteins":[26],"in":[27,44,72,122,179],"cancer":[28,39,125,151],"cells.":[29,46],"A":[30],"key":[31],"challenge":[32],"for":[33,130,170],"these":[34],"is":[36],"achieving":[37],"high":[38],"selectivity":[40,106],"prevent":[42],"toxicity":[43],"healthy":[45],"To":[47],"address":[48],"this":[49],"challenge,":[50],"we":[51],"present":[52],"novel":[54,167],"approach":[55],"combining":[56],"multiple":[57],"RAS":[58,76],"sensors":[59],"into":[60],"RAS-targeting":[61],"circuits,":[63],"which":[64,146],"allowed":[65],"us":[66],"an":[69],"output":[70,95,144],"protein":[71],"cells":[73,126,152],"with":[74,77,153],"unprecedented":[78],"selectivity.":[79],"We":[80,110],"implemented":[81],"modular":[83],"design":[84],"strategy":[85,169],"modeled":[87],"the":[88,102,113,117,138,159,174],"impact":[89],"of":[90,101,116,140,150,161,176],"individual":[91],"circuit":[92],"components":[93],"on":[94],"expression.":[96,109],"This":[97,156],"enabled":[98],"cell-line-specific":[99],"adaptation":[100],"optimize":[105],"fine-tune":[108],"further":[111],"demonstrate":[112],"targeting":[114],"capabilities":[115],"employing":[120],"them":[121,136],"different":[123],"RAS-driven":[124,171],"provide":[128],"evidence":[129],"their":[131],"potential":[133,160],"linking":[135],"expression":[139],"clinically":[142],"relevant":[143],"protein,":[145],"induced":[147],"robust":[148],"killing":[149],"RAS.":[155],"work":[157],"highlights":[158],"synthetic":[162,177],"as":[165],"cancers,":[172],"advancing":[173],"application":[175],"biology":[178],"oncology.":[180]},"counts_by_year":[{"year":2026,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2025-02-13T00:00:00"}