{"id":"https://openalex.org/W7224437222","doi":"https://doi.org/10.1261/rna.081254.126","title":"Antisense Oligonucleotides with 5\u2032-decoy technology triggers nonsense-mediated decay of SCN9A to elicit long-lasting analgesia","display_name":"Antisense Oligonucleotides with 5\u2032-decoy technology triggers nonsense-mediated decay of SCN9A to elicit long-lasting analgesia","publication_year":2026,"publication_date":"2026-10-29","ids":{"openalex":"https://openalex.org/W7224437222","doi":"https://doi.org/10.1261/rna.081254.126","pmid":"https://pubmed.ncbi.nlm.nih.gov/42957188"},"language":"en","primary_location":{"id":"doi:10.1261/rna.081254.126","doi":"https://doi.org/10.1261/rna.081254.126","is_oa":false,"landing_page_url":"https://doi.org/10.1261/rna.081254.126","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","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1"],"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/A5022102586","display_name":"Shaodong Meng","orcid":"https://orcid.org/0000-0001-9661-2754","observed_orcids":["https://orcid.org/0000-0001-9661-2754"]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Shaodong Meng","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":"https://orcid.org/0000-0001-9661-2754","affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160135396","display_name":"Xinyi Yang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xinyi Yang","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100362390","display_name":"Xuan Liu","orcid":"https://orcid.org/0009-0009-5004-2616","observed_orcids":["https://orcid.org/0009-0009-5004-2616"]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xuan Liu","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160110900","display_name":"Shangqing Li","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Shangqing Li","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160084809","display_name":"Yongkun Ma","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yongkun Ma","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100711621","display_name":"Xinli Wang","orcid":"https://orcid.org/0000-0002-1394-7418","observed_orcids":["https://orcid.org/0000-0002-1394-7418"]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xinli Wang","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160090031","display_name":"Haoyan Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Haoyan Zhang","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5137535112","display_name":"Rui Chen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Rui Chen","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065510770","display_name":"Zeb Azhar","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zeb Azhar","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160146161","display_name":"Yafei Guo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yafei Guo","raw_affiliation_strings":["Nanjing Normal University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University","institution_ids":["https://openalex.org/I152031979"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5049679131","display_name":"Qingyue Fu","orcid":"https://orcid.org/0009-0001-6654-2510","observed_orcids":["https://orcid.org/0009-0001-6654-2510"]},"institutions":[{"id":"https://openalex.org/I152031979","display_name":"Nanjing Normal University","ror":"https://ror.org/036trcv74","country_code":"CN","type":"education","lineage":["https://openalex.org/I152031979"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Qingyue Fu","raw_affiliation_strings":["Nanjing Normal University fuqingyue@nnu.edu.cn"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nanjing Normal University fuqingyue@nnu.edu.cn","institution_ids":["https://openalex.org/I152031979"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5049679131"],"corresponding_institution_ids":["https://openalex.org/I152031979"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.77245441,"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.081254.126","last_page":"rna.081254.126"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10604","display_name":"RNA Research and Splicing","score":0.5570999979972839,"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/T10604","display_name":"RNA Research and Splicing","score":0.5570999979972839,"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/T10725","display_name":"RNA Interference and Gene Delivery","score":0.31299999356269836,"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/T10493","display_name":"Ion channel regulation and function","score":0.021299999207258224,"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/antisense-oligonucleotides","display_name":"antisense oligonucleotides","score":0.9660000205039978},{"id":"https://openalex.org/keywords/scn9a","display_name":"SCN9A","score":0.9779999852180481},{"id":"https://openalex.org/keywords/nav1-7","display_name":"Nav1.7","score":0.9139999747276306},{"id":"https://openalex.org/keywords/nonsense-mediated-mrna-decay","display_name":"nonsense-mediated mRNA decay","score":0.8100000023841858},{"id":"https://openalex.org/keywords/alternative-splicing","display_name":"alternative splicing","score":0.9340000152587891},{"id":"https://openalex.org/keywords/frameshift-mutation","display_name":"frameshift mutation","score":0.7480000257492065},{"id":"https://openalex.org/keywords/u1-snrna","display_name":"U1 snRNA","score":0.7590000033378601},{"id":"https://openalex.org/keywords/elavl2","display_name":"ELAVL2","score":0.9639999866485596},{"id":"https://openalex.org/keywords/sr-proteins","display_name":"SR proteins","score":0.953000009059906},{"id":"https://openalex.org/keywords/rna-binding-proteins","display_name":"RNA-binding proteins","score":0.7459999918937683},{"id":"https://openalex.org/keywords/chronic-pain","display_name":"chronic pain","score":0.5609999895095825},{"id":"https://openalex.org/keywords/pain-relief","display_name":"analgesia","score":0.9739999771118164},{"id":"https://openalex.org/keywords/rna-targeted-therapeutics","display_name":"RNA-targeted therapeutics","score":0.7120000123977661},{"id":"https://openalex.org/keywords/isoform-selectivity","display_name":"isoform selectivity","score":0.7960000038146973}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8173999786376953},{"id":"https://openalex.org/C36823959","wikidata":"https://www.wikidata.org/wiki/Q373027","display_name":"Exon","level":3,"score":0.592199981212616},{"id":"https://openalex.org/C129312508","wikidata":"https://www.wikidata.org/wiki/Q133686","display_name":"Oligonucleotide","level":3,"score":0.5629000067710876},{"id":"https://openalex.org/C166703698","wikidata":"https://www.wikidata.org/wiki/Q201993","display_name":"RNA interference","level":4,"score":0.5461999773979187},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.5299999713897705},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4595000147819519},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4408999979496002},{"id":"https://openalex.org/C29906990","wikidata":"https://www.wikidata.org/wiki/Q1440688","display_name":"Frameshift mutation","level":4,"score":0.423799991607666},{"id":"https://openalex.org/C70219777","wikidata":"https://www.wikidata.org/wiki/Q14911527","display_name":"Nonsense-mediated decay","level":5,"score":0.3490999937057495},{"id":"https://openalex.org/C105580179","wikidata":"https://www.wikidata.org/wiki/Q188928","display_name":"Messenger RNA","level":3,"score":0.34869998693466187},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.33250001072883606},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.32670000195503235},{"id":"https://openalex.org/C53345823","wikidata":"https://www.wikidata.org/wiki/Q5531554","display_name":"Gene isoform","level":3,"score":0.3070000112056732},{"id":"https://openalex.org/C111829913","wikidata":"https://www.wikidata.org/wiki/Q211083","display_name":"Gene targeting","level":3,"score":0.2870999872684479},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.28700000047683716},{"id":"https://openalex.org/C22615655","wikidata":"https://www.wikidata.org/wiki/Q203221","display_name":"Small interfering RNA","level":4,"score":0.27630001306533813},{"id":"https://openalex.org/C2778776201","wikidata":"https://www.wikidata.org/wiki/Q3474283","display_name":"Exon skipping","level":5,"score":0.25200000405311584},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.25060001015663147},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.25049999356269836}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1261/rna.081254.126","doi":"https://doi.org/10.1261/rna.081254.126","is_oa":false,"landing_page_url":"https://doi.org/10.1261/rna.081254.126","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","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1"],"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:42957188","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42957188","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","id":"https://metadata.un.org/sdg/3","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7162991823","https://openalex.org/W1527748034","https://openalex.org/W4410579157","https://openalex.org/W7162402800","https://openalex.org/W2763205332","https://openalex.org/W7143536170","https://openalex.org/W1562626378","https://openalex.org/W7100045069","https://openalex.org/W2914831630","https://openalex.org/W7223130772"],"abstract_inverted_index":{"The":[0],"voltage-gated":[1],"sodium":[2],"channel":[3],"NaV1.7":[4],"(SCN9A)":[5],"is":[6,66],"a":[7,20,32,74,89,123,162,171],"genetically":[8],"validated":[9],"target":[10],"for":[11,23,166,175],"pain":[12,168],"therapy,":[13],"but":[14],"achieving":[15,73],"therapeutic":[16,164],"isoform":[17],"selectivity":[18],"remains":[19],"formidable":[21],"challenge":[22],"small-molecule":[24],"inhibitors.":[25],"Here,":[26],"we":[27,115],"overcome":[28],"this":[29],"bottleneck":[30],"through":[31],"highly":[33],"selective":[34],"RNA-targeted":[35],"strategy":[36],"that":[37,78,91],"dictates":[38],"SCN9A":[39],"alternative":[40],"splicing.":[41],"We":[42],"first":[43],"identified":[44],"ASO50":[45],"as":[46,161],"the":[47,98,117,127,137],"most":[48],"potent":[49],"baseline":[50],"candidate":[51],"antisense":[52],"oligonucleotide":[53],"(ASO).":[54],"Subsequent":[55],"5'-decoy":[56],"(5D)":[57],"sequence":[58],"screening":[59],"yielded":[60],"an":[61],"upgraded":[62],"candidate,":[63],"L9C-ASO50,":[64],"which":[65],"engineered":[67],"to":[68],"competitively":[69],"intercept":[70],"U1":[71],"snRNA,":[72],"cooperative":[75],"spatial":[76],"hindrance":[77],"robustly":[79],"suppresses":[80],"exon":[81,86,132],"5":[82],"recognition.":[83],"This":[84],"targeted":[85,177],"exclusion":[87],"introduces":[88],"frameshift":[90],"triggers":[92],"robust,":[93],"obligate":[94],"transcript":[95,159],"clearance":[96],"via":[97],"nonsense-mediated":[99],"mRNA":[100],"decay":[101],"(NMD)":[102],"pathway,":[103],"ensuring":[104],"complete":[105],"functional":[106],"silencing":[107],"without":[108],"cross-reacting":[109],"with":[110],"homologous":[111],"NaV":[112],"channels.":[113],"Mechanistically,":[114],"define":[116],"underlying":[118],"cis-trans":[119],"regulatory":[120],"architecture,":[121],"revealing":[122],"homeostatic":[124],"tug-of-war":[125],"where":[126],"RNA-binding":[128],"protein":[129,140],"ELAVL2":[130],"enforces":[131],"inclusion,":[133],"paradoxically":[134],"antagonized":[135],"by":[136],"canonical":[138],"SR":[139],"family.":[141],"Crucially,":[142],"CNS-restricted":[143],"delivery":[144],"of":[145],"L9C-ASO50":[146],"produces":[147],"profound":[148],"and":[149,152,169],"sustained":[150],"mechanical":[151],"thermal":[153],"analgesia.":[154],"These":[155],"findings":[156],"establish":[157],"splice-modulated":[158],"degradation":[160],"viable":[163],"paradigm":[165],"chronic":[167],"provide":[170],"broadly":[172],"applicable":[173],"blueprint":[174],"engineering":[176],"RNA":[178],"therapeutics.":[179]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2026-10-30T00:00:00"}