{"id":"https://openalex.org/W7204552941","doi":"https://doi.org/10.1261/rna.080982.126","title":"Improving the dynamic range of a trimethoprim-responsive self-amplifying RNA","display_name":"Improving the dynamic range of a trimethoprim-responsive self-amplifying RNA","publication_year":2026,"publication_date":"2026-08-28","ids":{"openalex":"https://openalex.org/W7204552941","doi":"https://doi.org/10.1261/rna.080982.126","pmid":"https://pubmed.ncbi.nlm.nih.gov/42665367"},"language":"en","primary_location":{"id":"doi:10.1261/rna.080982.126","doi":"https://doi.org/10.1261/rna.080982.126","is_oa":false,"landing_page_url":"https://doi.org/10.1261/rna.080982.126","pdf_url":null,"source":{"id":"https://openalex.org/S187657468","display_name":"RNA","issn_l":"1355-8382","issn":["1355-8382","1469-9001"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310315909","host_organization_name":"Cold Spring Harbor Laboratory Press","host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"RNA","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5013719758","display_name":"Pieter Vervaeke","orcid":"https://orcid.org/0000-0002-1297-3630","observed_orcids":["https://orcid.org/0000-0002-1297-3630"]},"institutions":[{"id":"https://openalex.org/I32597200","display_name":"Ghent University","ror":"https://ror.org/00cv9y106","country_code":"BE","type":"education","lineage":["https://openalex.org/I32597200"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Pieter Vervaeke","raw_affiliation_strings":["Universiteit Gent"],"raw_orcid":"https://orcid.org/0000-0002-1297-3630","affiliations":[{"raw_affiliation_string":"Universiteit Gent","institution_ids":["https://openalex.org/I32597200"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5024365503","display_name":"Francis Combes","orcid":"https://orcid.org/0000-0001-5926-4957","observed_orcids":["https://orcid.org/0000-0001-5926-4957"]},"institutions":[{"id":"https://openalex.org/I4387930256","display_name":"SINTEF Industry","ror":"https://ror.org/0422tvz87","country_code":"NO","type":"facility","lineage":["https://openalex.org/I173888879","https://openalex.org/I4387930256"]}],"countries":["NO"],"is_corresponding":false,"raw_author_name":"Francis Combes","raw_affiliation_strings":["SINTEF Industri"],"raw_orcid":"https://orcid.org/0000-0001-5926-4957","affiliations":[{"raw_affiliation_string":"SINTEF Industri","institution_ids":["https://openalex.org/I4387930256"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5081121290","display_name":"Niek N. Sanders","orcid":"https://orcid.org/0000-0003-4585-0343","observed_orcids":["https://orcid.org/0000-0003-4585-0343"]},"institutions":[{"id":"https://openalex.org/I32597200","display_name":"Ghent University","ror":"https://ror.org/00cv9y106","country_code":"BE","type":"education","lineage":["https://openalex.org/I32597200"]}],"countries":["BE"],"is_corresponding":true,"raw_author_name":"Niek Sanders","raw_affiliation_strings":["Universiteit Gent; niek.sanders@ugent.be"],"raw_orcid":"https://orcid.org/0000-0003-4585-0343","affiliations":[{"raw_affiliation_string":"Universiteit Gent; niek.sanders@ugent.be","institution_ids":["https://openalex.org/I32597200"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5081121290"],"corresponding_institution_ids":["https://openalex.org/I32597200"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.61899499,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"rna.080982.126","last_page":"rna.080982.126"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10725","display_name":"RNA Interference and Gene Delivery","score":0.47749999165534973,"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/T10725","display_name":"RNA Interference and Gene Delivery","score":0.47749999165534973,"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/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.46070000529289246,"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/T10604","display_name":"RNA Research and Splicing","score":0.03999999910593033,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/self-amplifying-mrna","display_name":"self-amplifying mRNA","score":0.953000009059906},{"id":"https://openalex.org/keywords/trimethoprim","display_name":"trimethoprim","score":0.8840000033378601},{"id":"https://openalex.org/keywords/dynamic-range","display_name":"dynamic range","score":0.7580000162124634},{"id":"https://openalex.org/keywords/l7ae","display_name":"L7Ae","score":0.765999972820282},{"id":"https://openalex.org/keywords/protein-replacement-therapy","display_name":"protein replacement therapy","score":0.5270000100135803},{"id":"https://openalex.org/keywords/3-untranslated-region","display_name":"3' untranslated region","score":0.8389999866485596},{"id":"https://openalex.org/keywords/mechanistic-modeling","display_name":"mechanistic modeling","score":0.6610000133514404}],"concepts":[{"id":"https://openalex.org/C189819185","wikidata":"https://www.wikidata.org/wiki/Q384283","display_name":"Subgenomic mRNA","level":4,"score":0.8090999722480774},{"id":"https://openalex.org/C51785407","wikidata":"https://www.wikidata.org/wiki/Q2627568","display_name":"Effector","level":2,"score":0.8040000200271606},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.786899983882904},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.5913000106811523},{"id":"https://openalex.org/C105580179","wikidata":"https://www.wikidata.org/wiki/Q188928","display_name":"Messenger RNA","level":3,"score":0.534500002861023},{"id":"https://openalex.org/C3675279","wikidata":"https://www.wikidata.org/wiki/Q211935","display_name":"Protein biosynthesis","level":2,"score":0.5008000135421753},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.48420000076293945},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.45649999380111694},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.44519999623298645},{"id":"https://openalex.org/C144292202","wikidata":"https://www.wikidata.org/wiki/Q898273","display_name":"Protein domain","level":3,"score":0.4203000068664551},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.350600004196167},{"id":"https://openalex.org/C6856738","wikidata":"https://www.wikidata.org/wiki/Q331672","display_name":"Protein expression","level":3,"score":0.3440999984741211},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.3257000148296356},{"id":"https://openalex.org/C2993175405","wikidata":"https://www.wikidata.org/wiki/Q8054","display_name":"Bacterial protein","level":3,"score":0.3091999888420105},{"id":"https://openalex.org/C97702854","wikidata":"https://www.wikidata.org/wiki/Q4039747","display_name":"Guide RNA","level":5,"score":0.30149999260902405},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.29820001125335693},{"id":"https://openalex.org/C47701112","wikidata":"https://www.wikidata.org/wiki/Q735188","display_name":"Protein structure","level":2,"score":0.2930999994277954},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.28349998593330383},{"id":"https://openalex.org/C147816474","wikidata":"https://www.wikidata.org/wiki/Q169525","display_name":"Protein engineering","level":3,"score":0.2768999934196472},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.275299996137619},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.273499995470047},{"id":"https://openalex.org/C87133666","wikidata":"https://www.wikidata.org/wiki/Q1161699","display_name":"Dynamic range","level":2,"score":0.2727000117301941},{"id":"https://openalex.org/C204323151","wikidata":"https://www.wikidata.org/wiki/Q905424","display_name":"Range (aeronautics)","level":2,"score":0.2648000121116638},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.25760000944137573},{"id":"https://openalex.org/C142613039","wikidata":"https://www.wikidata.org/wiki/Q272983","display_name":"Green fluorescent protein","level":3,"score":0.2556000053882599},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.25209999084472656},{"id":"https://openalex.org/C149364088","wikidata":"https://www.wikidata.org/wiki/Q185917","display_name":"Translation (biology)","level":4,"score":0.2515000104904175}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1261/rna.080982.126","doi":"https://doi.org/10.1261/rna.080982.126","is_oa":false,"landing_page_url":"https://doi.org/10.1261/rna.080982.126","pdf_url":null,"source":{"id":"https://openalex.org/S187657468","display_name":"RNA","issn_l":"1355-8382","issn":["1355-8382","1469-9001"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-2","ki-jl-2","medline","norway-2"],"host_organization":"https://openalex.org/P4310315909","host_organization_name":"Cold Spring Harbor Laboratory Press","host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"RNA","raw_type":"journal-article"},{"id":"pmid:42665367","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42665367","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":"RNA (New York, N.Y.)","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.46810001134872437,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Self-amplifying":[0],"mRNA":[1],"(SAM)":[2],"is":[3],"a":[4,17,45,67,77,92,113,147],"potential":[5],"platform":[6,155],"for":[7,20],"protein":[8,19,33,63,74,123],"replacement,":[9],"as":[10,49],"it":[11],"enables":[12],"recipients":[13],"to":[14,76,110],"transiently":[15],"produce":[16],"therapeutic":[18],"4-8":[21],"weeks.":[22],"To":[23],"obtain":[24],"external":[25],"control":[26],"over":[27],"the":[28,42,56,61,72,88,95,100,117,154],"level":[29,121],"and":[30,120,150],"duration":[31],"of":[32,44,65,94,99,122,129,136,153],"expression,":[34],"synthetic":[35],"SAM":[36,69,96],"constructs":[37],"that":[38,106,134],"switch":[39],"OFF":[40],"in":[41,55,139,146],"presence":[43],"small":[46],"molecule":[47],"such":[48,66],"trimethoprim":[50],"(TMP)":[51],"have":[52],"been":[53],"developed":[54],"past.":[57],"Here,":[58],"we":[59],"increase":[60],"ON-state":[62],"expression":[64],"TMP-responsive":[68,78],"by":[70,90],"fusing":[71,107],"effector":[73],"L7Ae":[75,111],"destabilizing":[79],"domain":[80],"(DD)":[81],"on":[82,116],"both":[83],"terminals.":[84],"We":[85,104,131],"also":[86],"lower":[87],"OFF-state":[89],"adding":[91],"duplicate":[93],"3'UTR":[97],"downstream":[98],"DD-L7Ae":[101,137],"subgenomic":[102],"ORF.":[103],"demonstrate":[105,133],"two":[108],"DDs":[109],"has":[112],"beneficial":[114],"effect":[115],"response":[118],"rate":[119],"production":[124],"after":[125],"removal":[126],"or":[127],"addition":[128],"TMP.":[130],"further":[132,151],"overexpression":[135],"results":[138],"microscopic":[140],"abnormalities.":[141],"These":[142],"insights":[143],"are":[144,156],"implemented":[145],"mechanistic":[148],"model,":[149],"improvements":[152],"highlighted.":[157]},"counts_by_year":[],"updated_date":"2026-08-30T07:30:35.949966","created_date":"2026-08-29T00:00:00"}