{"id":"https://openalex.org/W4389230992","doi":"https://doi.org/10.1182/blood-2023-182468","title":"Development of an Ex Vivo Precision Gene Engineered B Cell Medicine That Produces Active and Sustained Levels of FIX for the Treatment of Hemophilia B","display_name":"Development of an Ex Vivo Precision Gene Engineered B Cell Medicine That Produces Active and Sustained Levels of FIX for the Treatment of Hemophilia B","publication_year":2023,"publication_date":"2023-11-02","ids":{"openalex":"https://openalex.org/W4389230992","doi":"https://doi.org/10.1182/blood-2023-182468"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2023-182468","doi":"https://doi.org/10.1182/blood-2023-182468","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2023-182468","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"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/A5061268748","display_name":"Hanlan Liu","orcid":"https://orcid.org/0009-0003-7724-9103","observed_orcids":["https://orcid.org/0009-0003-7724-9103"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hanlan Liu","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063365061","display_name":"Swati Singh","orcid":"https://orcid.org/0000-0001-7420-9438","observed_orcids":["https://orcid.org/0000-0001-7420-9438"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Swati Singh","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064696929","display_name":"Timothy Mullen","orcid":"https://orcid.org/0000-0002-0486-3167","observed_orcids":["https://orcid.org/0000-0002-0486-3167","https://orcid.org/0000-0001-5820-4071"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Timothy Mullen","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042107018","display_name":"Caroline Bullock","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Caroline Bullock","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004091625","display_name":"Sean Keegan","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sean Keegan","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028512226","display_name":"Troy D. Patterson","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Troy Patterson","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057717066","display_name":"Amy Lundberg","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Amy Lundberg","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":null,"display_name":"Sakshisingh Thakur","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sakshisingh Thakur","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002968571","display_name":"Charuta Yadav","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Charuta Yadav","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073821295","display_name":"Shamael R. Dastagir","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shamael Dastagir","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100361075","display_name":"Lily Li","orcid":"https://orcid.org/0000-0001-9844-7692","observed_orcids":["https://orcid.org/0000-0001-9844-7692"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lily Li","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077648255","display_name":"Wayne Bainter","orcid":"https://orcid.org/0000-0003-2032-8348","observed_orcids":["https://orcid.org/0000-0003-2032-8348"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Wayne Bainter","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5093396024","display_name":"Shalini Chilakala","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shalini Chilakala","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059531643","display_name":"Anja F. Hohmann","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Anja Hohmann","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061430138","display_name":"Adam S. Lazorchak","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Adam Lazorchak","raw_affiliation_strings":["1Be Biopharma, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Be Biopharma, Cambridge, MA","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5103494767","display_name":"Richard A. Morgan","orcid":"https://orcid.org/0009-0006-6584-2382","observed_orcids":["https://orcid.org/0009-0006-6584-2382"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Richard A Morgan","raw_affiliation_strings":["2Be Biopharma, Center Harbor, NH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Be Biopharma, Center Harbor, NH","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5000,"currency":"USD","value_usd":5000},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":5,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"142","issue":"Supplement 1","first_page":"463","last_page":"463"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11280","display_name":"Hemophilia Treatment and Research","score":0.9945999979972839,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11280","display_name":"Hemophilia Treatment and Research","score":0.9945999979972839,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10613","display_name":"Virus-based gene therapy research","score":0.003800000064074993,"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/T11491","display_name":"CAR-T cell therapy research","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hemophilia-b","display_name":"hemophilia B","score":0.9860000014305115},{"id":"https://openalex.org/keywords/factor-ix","display_name":"factor IX","score":0.9279999732971191},{"id":"https://openalex.org/keywords/crispr-cas9-genome-editing","display_name":"CRISPR/Cas9 genome editing","score":0.8370000123977661},{"id":"https://openalex.org/keywords/plasma-cell-differentiation","display_name":"plasma cell differentiation","score":0.8090000152587891},{"id":"https://openalex.org/keywords/recombinant-factor-ix","display_name":"recombinant factor IX","score":0.6650000214576721},{"id":"https://openalex.org/keywords/gamma-carboxylation","display_name":"gamma-carboxylation","score":0.49900001287460327},{"id":"https://openalex.org/keywords/vitamin-k","display_name":"vitamin K","score":0.3630000054836273}],"concepts":[{"id":"https://openalex.org/C2781221834","wikidata":"https://www.wikidata.org/wiki/Q425360","display_name":"Factor IX","level":2,"score":0.7816988229751587},{"id":"https://openalex.org/C111599444","wikidata":"https://www.wikidata.org/wiki/Q213901","display_name":"Genetic enhancement","level":3,"score":0.7547909021377563},{"id":"https://openalex.org/C26291073","wikidata":"https://www.wikidata.org/wiki/Q310484","display_name":"Ex vivo","level":3,"score":0.6743940114974976},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6637861728668213},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.5365166068077087},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.5279577970504761},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.4976504147052765},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.41519638895988464},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3665943741798401},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.3304431438446045},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.26905524730682373},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2671586871147156},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.22932294011116028},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.11211875081062317},{"id":"https://openalex.org/C99454951","wikidata":"https://www.wikidata.org/wiki/Q932068","display_name":"Environmental health","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2023-182468","doi":"https://doi.org/10.1182/blood-2023-182468","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2023-182468","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"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/W4414015823","https://openalex.org/W4406843834","https://openalex.org/W2276008310","https://openalex.org/W3216150095","https://openalex.org/W4318988282","https://openalex.org/W2775732184","https://openalex.org/W4311860699","https://openalex.org/W7098688569","https://openalex.org/W4417006142","https://openalex.org/W2899078923"],"abstract_inverted_index":{"Hemophilia":[0],"B":[1,43,175,178,253,479],"is":[2,14,45,226],"an":[3,30,70,117,214,235,473],"X-linked":[4],"recessive":[5],"bleeding":[6],"disorder":[7],"that":[8,22,482],"affects":[9],"approximately":[10,306],"1:20,000":[11],"males.":[12],"It":[13],"caused":[15],"by":[16,260,265,312,336,342],"mutations":[17],"in":[18,33,100,301,381,383,403,418,421,432,462],"the":[19,25,34,139,144,200,208,218,277,296,360,384,437,452,491],"F9":[20,274],"gene":[21,75,159,275,477],"encodes":[23],"for":[24,41,82,131,135,162,187,190,217,490,512],"factor":[26,114],"IX":[27],"(FIX)":[28],"protein,":[29,327],"essential":[31],"enzyme":[32],"coagulation":[35],"cascade.":[36],"The":[37,55,287,405,448,496],"current":[38],"recommended":[39],"therapy":[40,160],"hemophilia":[42,101,494,513],"patients":[44,121,152],"prophylactic":[46],"administration":[47],"of":[48,59,105,146,193,197,221,272,325,330,348,371,407,436,455,488,493,500],"exogenous":[49],"FIX":[50,60,147,326,339,349,396,438,489],"derived":[51,171],"from":[52,172],"recombinant":[53],"protein.":[54],"short":[56],"biological":[57,369],"half-life":[58],"requires":[61],"frequent":[62],"infusions":[63,104],"to":[64,120,149,202,210,228,321,367],"maintain":[65],"therapeutic":[66,230,246,498],"level.":[67],"More":[68],"recently,":[69],"adeno-associated":[71],"virus":[72],"(AAV)":[73],"vector-based":[74],"therapy,":[76,126],"etranacogene":[77],"dezaparvovec,":[78],"has":[79,410],"been":[80,411],"approved":[81],"some":[83],"adults":[84],"as":[85,153,310,334],"a":[86,95,128,445,508],"potential":[87,134,497],"new":[88],"option.":[89],"Despite":[90],"these":[91],"advances,":[92],"there":[93],"remains":[94],"significant":[96,136],"unmet":[97],"medical":[98],"need":[99],"B.":[102,495,514],"Intravenous":[103],"weekly":[106],"(or":[107],"more":[108],"frequently,":[109],"3":[110],"times":[111],"per":[112],"week)":[113],"replacements":[115],"are":[116],"enormous":[118],"burden":[119],"and":[122,207,244,258,293,416,460,485],"their":[123],"caregivers.":[124],"Gene":[125],"while":[127],"promising":[129],"option":[130],"some,":[132],"carries":[133],"risk.":[137],"Importantly,":[138],"limitations":[140],"associated":[141],"with":[142,242,395],"increasing":[143],"dose":[145],"needed":[148],"treat":[150],"pediatric":[151],"they":[154],"age":[155],"make":[156],"immunogenic":[157],"AAV-based":[158],"inappropriate":[161],"this":[163,249,501],"patient":[164],"population.":[165],"Terminally":[166],"differentiated":[167,294],"human":[168,252,273],"plasma":[169,297],"cells":[170,176,254,288],"genetically":[173],"engineered":[174,239,259,478],"(termed":[177],"Cell":[179],"Medicines,":[180],"BeCMs),":[181],"potentially":[182],"offer":[183],"natural":[184],"longevity":[185],"(persisting":[186],"decades),":[188],"capacity":[189],"high":[191],"levels":[192,487],"protein":[194,350],"secretion":[195,332],"(thousands":[196],"Ig":[198],"molecules/cell/sec),":[199],"ability":[201,209],"engraft":[203,459],"without":[204],"host":[205],"preconditioning,":[206],"re-dose,":[211],"making":[212],"them":[213],"attractive":[215],"platform":[216,241],"sustained":[219,486],"supply":[220],"biologics":[222],"where":[223],"continuous":[224],"dosing":[225],"required":[227],"achieve":[229],"benefit.":[231],"We":[232,304],"have":[233,471],"developed":[234,472],"ex":[236,474],"vivo":[237,419,475],"precision":[238,476],"BeCM":[240,440],"modularity":[243],"broad":[245],"utility.":[247],"In":[248,468],"study,":[250],"primary":[251],"were":[255,289,389,430],"isolated,":[256],"activated,":[257],"CRISPR/Cas9":[261],"genome":[262],"editing":[263],"followed":[264],"AAV-mediated":[266],"homology":[267],"directed":[268],"repair":[269],"(HDR)":[270],"insertion":[271],"into":[276,391],"C-C":[278],"chemokine":[279],"receptor":[280],"type":[281],"5":[282],"(CCR5)":[283],"safe":[284],"harbor":[285],"locus.":[286],"then":[290],"further":[291],"expanded":[292],"towards":[295],"cell":[298,480],"lineage,":[299],"resulting":[300],"FIX-producing":[302],"BeCMs.":[303],"achieved":[305],"40%":[307,329],"targeted":[308],"integration":[309],"measured":[311,335],"droplet":[313],"digital":[314],"PCR":[315],"(ddPCR).":[316],"Engineered":[317],"BeCMs":[318,376,388,409],"secreted":[319],"up":[320],"60":[322],"ng/1e6":[323],"cells/hour":[324],"approaching":[328],"IgG":[331],"rate":[333],"ELISA.":[337],"BeCM-produced":[338,372],"was":[340,365,442],"analyzed":[341],"LC-MS":[343],"which":[344,458],"demonstrated":[345,398],"gamma":[346],"carobxylation":[347],"Gal-domain.":[351],"Vitamin":[352],"K-dependent":[353,379],"activated":[354],"partial":[355],"thromboplastin":[356],"time":[357],"(aPTT),":[358],"using":[359,444],"one":[361],"stage":[362],"clotting":[363],"assay,":[364],"employed":[366],"verify":[368],"activity":[370,380],"FIX.":[373],"Similarly,":[374],"FIX-expressing":[375,387,408,456],"exhibited":[377],"vitamin":[378],"vitro":[382],"chromogenic":[385],"assay.":[386,447],"transferred":[390],"immunodeficient":[392],"NOG-hIL6":[393,422],"mice,":[394],"production":[397],"at":[399],"least":[400],"20":[401],"weeks":[402],"vivo.":[404],"safety":[406],"characterized":[412],"based":[413],"on":[414],"28-day":[415],"5-month":[417],"studies":[420],"mice.":[423],"Neither":[424],"abnormal":[425],"clinical":[426],"observations":[427],"nor":[428],"mortality":[429],"observed":[431],"those":[433],"studies.":[434],"Biodistribution":[435],"expressing":[439],"product":[441],"assessed":[443],"qPCR":[446,449],"data":[450],"confirms":[451],"expected":[453],"biodistribution":[454],"BeCMs,":[457],"persist":[461],"bone":[463],"marrow":[464],"tissue":[465],"over":[466],"time.":[467],"summary,":[469],"we":[470],"medicine":[481],"produces":[483],"active":[484],"treatment":[492,510],"application":[499],"unique":[502],"biologic":[503],"delivery":[504],"system":[505],"could":[506],"afford":[507],"novel":[509],"modality":[511]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":2}],"updated_date":"2026-11-13T13:42:25.865203","created_date":"2023-12-02T00:00:00"}