{"id":"https://openalex.org/W7225827769","doi":"https://doi.org/10.64898/2026.11.09.765359","title":"Reprogramming transcription factor networks with a HOX inhibitor to address Huntington\u2032s disease biology beyond mutant huntingtin","display_name":"Reprogramming transcription factor networks with a HOX inhibitor to address Huntington\u2032s disease biology beyond mutant huntingtin","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225827769","doi":"https://doi.org/10.64898/2026.11.09.765359"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.09.765359","doi":"https://doi.org/10.64898/2026.11.09.765359","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.09.765359","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.11.09.765359","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5044429339","display_name":"Michael Klukinov","orcid":"https://orcid.org/0000-0002-5229-6777","observed_orcids":["https://orcid.org/0000-0002-5229-6777"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael Klukinov","raw_affiliation_strings":["Core Biotherapeutics, Inc.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Core Biotherapeutics, Inc.;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160012150","display_name":"Rick Orr","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rick Orr","raw_affiliation_strings":["Core Biotherapeutics, Inc.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Core Biotherapeutics, Inc.;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160039429","display_name":"William K Martin","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"William K. Martin","raw_affiliation_strings":["Core Biotherapeutics, Inc.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Core Biotherapeutics, Inc.;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109662545","display_name":"Shashidar H. Kori","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shashidar Kori","raw_affiliation_strings":["Core Biotherapeutics, Inc.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Core Biotherapeutics, Inc.;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006869407","display_name":"David C. Yeomans","orcid":"https://orcid.org/0000-0002-9389-8539","observed_orcids":["https://orcid.org/0000-0002-9389-8539"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"David C. Yeomans","raw_affiliation_strings":["Core Biotherapeutics, Inc.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Core Biotherapeutics, Inc.;","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5110183168","display_name":"Julien Mamet","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Julien Mamet","raw_affiliation_strings":["Core Biotherapeutics, Inc"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Core Biotherapeutics, Inc","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5110183168"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10949","display_name":"Genetic Neurodegenerative Diseases","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10949","display_name":"Genetic Neurodegenerative Diseases","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11772","display_name":"Genetics and Neurodevelopmental Disorders","score":0.0003000000142492354,"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/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C111039654","wikidata":"https://www.wikidata.org/wiki/Q253149","display_name":"Hox gene","level":4,"score":0.9072999954223633},{"id":"https://openalex.org/C2781427258","wikidata":"https://www.wikidata.org/wiki/Q2620886","display_name":"Huntingtin","level":4,"score":0.8912000060081482},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.809499979019165},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.6890000104904175},{"id":"https://openalex.org/C166252455","wikidata":"https://www.wikidata.org/wiki/Q6736610","display_name":"Trinucleotide repeat expansion","level":4,"score":0.6391000151634216},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5860000252723694},{"id":"https://openalex.org/C77255625","wikidata":"https://www.wikidata.org/wiki/Q402093","display_name":"Reprogramming","level":3,"score":0.5752999782562256},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.5691999793052673},{"id":"https://openalex.org/C2910011555","wikidata":"https://www.wikidata.org/wiki/Q2620886","display_name":"Huntingtin Protein","level":5,"score":0.5260999798774719},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.5042999982833862},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.43790000677108765},{"id":"https://openalex.org/C134305767","wikidata":"https://www.wikidata.org/wiki/Q725508","display_name":"Somatic cell","level":3,"score":0.4120999872684479},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.3808000087738037},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.3662000000476837},{"id":"https://openalex.org/C121587040","wikidata":"https://www.wikidata.org/wiki/Q898769","display_name":"Homeobox","level":4,"score":0.3452000021934509},{"id":"https://openalex.org/C151913843","wikidata":"https://www.wikidata.org/wiki/Q3454555","display_name":"Dominance (genetics)","level":3,"score":0.3434000015258789},{"id":"https://openalex.org/C2780647506","wikidata":"https://www.wikidata.org/wiki/Q190564","display_name":"Huntington's disease","level":3,"score":0.32109999656677246},{"id":"https://openalex.org/C179926584","wikidata":"https://www.wikidata.org/wiki/Q207714","display_name":"Transcription (linguistics)","level":2,"score":0.29089999198913574},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.2847000062465668},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.2824999988079071},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.2800000011920929},{"id":"https://openalex.org/C53345823","wikidata":"https://www.wikidata.org/wiki/Q5531554","display_name":"Gene isoform","level":3,"score":0.26600000262260437},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.260699987411499},{"id":"https://openalex.org/C105951970","wikidata":"https://www.wikidata.org/wiki/Q1036748","display_name":"Loss function","level":4,"score":0.25540000200271606},{"id":"https://openalex.org/C111936080","wikidata":"https://www.wikidata.org/wiki/Q913367","display_name":"Enhancer","level":4,"score":0.2542000114917755}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.09.765359","doi":"https://doi.org/10.64898/2026.11.09.765359","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.09.765359","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.09.765359","doi":"https://doi.org/10.64898/2026.11.09.765359","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.09.765359","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[],"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":{"Huntington\u2032s":[0],"disease":[1,44,134],"(HD)":[2],"is":[3,80],"an":[4],"inherited":[5,20,117],"neurodegenerative":[6],"disorder":[7],"caused":[8],"by":[9],"CAG-repeat":[10,21,118],"expansion":[11],"in":[12,88,96,150,198,210],"the":[13,24,48,77,81,191,216,225],"huntingtin":[14,165],"(":[15],"HTT":[16],")":[17],"gene.":[18],"Although":[19],"length":[22],"and":[23,69,92,115,131,136,157,174,203,206],"underlying":[25],"somatic":[26,236],"instability":[27],"are":[28,108],"key":[29],"determinants":[30],"of":[31,39,99,122,163,194,220],"age":[32,128],"at":[33,111,116,129],"onset,":[34],"they":[35],"explain":[36],"only":[37,82,169],"part":[38],"onset":[40,130],"variability,":[41],"suggesting":[42],"additional":[43],"mechanisms.":[45],"We":[46],"applied":[47],"Core":[49],"Coefficient":[50],"(CC),":[51],"a":[52,142,181],"transcription-factor":[53],"(TF)":[54],"network-decoding":[55],"technology":[56],"that":[57,84,229],"quantifies":[58],"TF":[59,75],"functional":[60,94,192],"dominance,":[61],"to":[62,223],">100":[63],"post-mortem":[64],"neuronal":[65,151,199],"transcriptomes":[66],"from":[67],"HD":[68,101],"control":[70],"brain":[71,103],"datasets.":[72],"Among":[73],"human":[74],"families,":[76],"HOX":[78,106,123,139,172,182,221],"family":[79,83],"uniformly":[85],"exhibits":[86],"quiescence":[87],"controls":[89],"versus":[90],"large":[91],"significant":[93],"dominance":[95,173,193],"vulnerable":[97],"neurons":[98],"each":[100],"donor":[102],"we":[104],"investigated.":[105],"TFs":[107,140,222],"already":[109],"dominant":[110],"Vonsattel":[112],"grade":[113,135],"0":[114],"length.":[119],"The":[120],"magnitude":[121],"CC":[124],"values":[125],"correlates":[126],"with":[127,133],"increases":[132],"CAG-Age":[137],"Product.":[138],"form":[141],"self-sustained":[143],"pathological":[144],"unit":[145],"targeting":[146],">4,000":[147],"genes":[148],"implicated":[149],"patterning,":[152,205],"identity,":[153],"stress,":[154],"signaling,":[155],"structure,":[156],"senescence.":[158],"In":[159],"zQ175":[160],"mice,":[161],"abrogation":[162],"mutant":[164],"(mHTT)":[166],"protein":[167],"production":[168],"transiently":[170],"attenuates":[171],"does":[175],"not":[176],"durably":[177],"eliminate":[178],"it.":[179],"COR-H800,":[180],"inhibitor,":[183],"restored":[184],"TF-network":[185],"hierarchy":[186],"toward":[187],"wild":[188],"type,":[189],"normalizing":[190],"transcription":[195],"factors":[196],"involved":[197],"differentiation,":[200],"cell-fate":[201],"determination,":[202],"developmental":[204],"improved":[207],"disease-relevant":[208],"phenotypes":[209],"R6/2":[211],"mice.":[212],"These":[213],"findings":[214],"support":[215],"direct":[217],"selective":[218],"inhibition":[219],"address":[224],"aberrant":[226],"transcriptional":[227],"state":[228],"can":[230],"persist":[231],"despite":[232],"mHTT":[233],"lowering":[234],"or":[235],"instability-targeted":[237],"therapeutic":[238],"interventions.":[239]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}