{"id":"https://openalex.org/W2563250258","doi":"https://doi.org/10.1016/s1525-0016(16)33941-7","title":"332. ZFN-Mediated Minigene or Dinucleotide Gene Correction of p47phox Deficient Autosomal Recessive Chronic Granulomatous Disease iPSC to Generate Oxidase Functional Neutrophils","display_name":"332. ZFN-Mediated Minigene or Dinucleotide Gene Correction of p47phox Deficient Autosomal Recessive Chronic Granulomatous Disease iPSC to Generate Oxidase Functional Neutrophils","publication_year":2015,"publication_date":"2015-05-01","ids":{"openalex":"https://openalex.org/W2563250258","doi":"https://doi.org/10.1016/s1525-0016(16)33941-7","mag":"2563250258"},"language":"en","primary_location":{"id":"doi:10.1016/s1525-0016(16)33941-7","doi":"https://doi.org/10.1016/s1525-0016(16)33941-7","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s1525-0016(16)33941-7","pdf_url":"http://www.cell.com/article/S1525001616339417/pdf","source":{"id":"https://openalex.org/S51596929","display_name":"Molecular Therapy","issn_l":"1525-0016","issn":["1525-0016","1525-0024"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-1","poland-140","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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Therapy","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"http://www.cell.com/article/S1525001616339417/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5042474944","display_name":"Randall K. Merling","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210134534","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Randall K. Merling","raw_affiliation_strings":["Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088738110","display_name":"Suk See De Ravin","orcid":"https://orcid.org/0000-0002-9800-774X","observed_orcids":["https://orcid.org/0000-0002-9800-774X"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210134534","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Suk See De Ravin","raw_affiliation_strings":["Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047938723","display_name":"Colin L. Sweeney","orcid":"https://orcid.org/0000-0002-9442-1134","observed_orcids":["https://orcid.org/0000-0002-9442-1134"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210134534","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Colin L. Sweeney","raw_affiliation_strings":["Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5018910683","display_name":"Douglas Byron Kuhns","orcid":"https://orcid.org/0000-0002-9971-0760","observed_orcids":["https://orcid.org/0000-0002-9971-0760"]},"institutions":[{"id":"https://openalex.org/I4396570585","display_name":"Leidos Biomedical Research Inc. (United States)","ror":"https://ror.org/00bardy64","country_code":"US","type":"company","lineage":["https://openalex.org/I114662689","https://openalex.org/I4396570585"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Douglas B. Kuhns","raw_affiliation_strings":["Neutrophil Monitoring Lab, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., NIAID/NIH, Frederick, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neutrophil Monitoring Lab, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., NIAID/NIH, Frederick, MD","institution_ids":["https://openalex.org/I4396570585"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103389644","display_name":"Giovanni Di Pasquale","orcid":"https://orcid.org/0009-0006-7818-4040","observed_orcids":["https://orcid.org/0009-0006-7818-4040"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210088259","display_name":"National Institute of Dental and Craniofacial Research","ror":"https://ror.org/004a2wv92","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210088259"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Giovanni Di Pasquale","raw_affiliation_strings":["Adeno-Associated Virus Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Adeno-Associated Virus Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210088259"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054422575","display_name":"John A. Chiorini","orcid":"https://orcid.org/0000-0003-4919-4056","observed_orcids":["https://orcid.org/0000-0003-4919-4056"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210088259","display_name":"National Institute of Dental and Craniofacial Research","ror":"https://ror.org/004a2wv92","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210088259"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John A. Chiorini","raw_affiliation_strings":["Adeno-Associated Virus Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Adeno-Associated Virus Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210088259"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5013149726","display_name":"Harry L. Malech","orcid":"https://orcid.org/0000-0001-5874-5775","observed_orcids":["https://orcid.org/0000-0001-5874-5775"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210134534","display_name":"National Institute of Allergy and Infectious Diseases","ror":"https://ror.org/043z4tv69","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Harry L. Malech","raw_affiliation_strings":["Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Host Defenses, NIAID/NIH, Bethesda, MD","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210134534"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":{"value":4500,"currency":"USD","value_usd":4500},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.19434611,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"23","issue":null,"first_page":"S133","last_page":"S133"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10878","display_name":"CRISPR and Genetic Engineering","score":0.9082000255584717,"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/T10878","display_name":"CRISPR and Genetic Engineering","score":0.9082000255584717,"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/T11725","display_name":"Immunodeficiency and Autoimmune Disorders","score":0.025299999862909317,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11597","display_name":"Neutrophil, Myeloperoxidase and Oxidative Mechanisms","score":0.018200000748038292,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/zinc-finger-nucleases","display_name":"zinc finger nucleases","score":0.9430000185966492},{"id":"https://openalex.org/keywords/minigene","display_name":"minigene","score":0.718999981880188},{"id":"https://openalex.org/keywords/induced-pluripotent-stem-cells","display_name":"induced pluripotent stem cells","score":0.9319999814033508},{"id":"https://openalex.org/keywords/nadph-oxidase","display_name":"NADPH oxidase","score":0.8240000009536743},{"id":"https://openalex.org/keywords/reactive-oxygen-species","display_name":"reactive oxygen species","score":0.6970000267028809},{"id":"https://openalex.org/keywords/aav2-vector","display_name":"AAV2 vector","score":0.5640000104904175},{"id":"https://openalex.org/keywords/gene-therapy","display_name":"gene therapy","score":0.3319999873638153}],"concepts":[{"id":"https://openalex.org/C166342232","wikidata":"https://www.wikidata.org/wiki/Q11936831","display_name":"Minigene","level":5,"score":0.9065953493118286},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8347128629684448},{"id":"https://openalex.org/C2778175462","wikidata":"https://www.wikidata.org/wiki/Q2165663","display_name":"Chronic granulomatous disease","level":2,"score":0.6977018117904663},{"id":"https://openalex.org/C36823959","wikidata":"https://www.wikidata.org/wiki/Q373027","display_name":"Exon","level":3,"score":0.6493360996246338},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.5081126689910889},{"id":"https://openalex.org/C2779390119","wikidata":"https://www.wikidata.org/wiki/Q917227","display_name":"Sandhoff disease","level":3,"score":0.5014379024505615},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4967520833015442},{"id":"https://openalex.org/C29906990","wikidata":"https://www.wikidata.org/wiki/Q1440688","display_name":"Frameshift mutation","level":4,"score":0.43734705448150635},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.34118711948394775},{"id":"https://openalex.org/C194583182","wikidata":"https://www.wikidata.org/wiki/Q21114084","display_name":"Alternative splicing","level":4,"score":0.1392025649547577}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1016/s1525-0016(16)33941-7","doi":"https://doi.org/10.1016/s1525-0016(16)33941-7","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s1525-0016(16)33941-7","pdf_url":"http://www.cell.com/article/S1525001616339417/pdf","source":{"id":"https://openalex.org/S51596929","display_name":"Molecular Therapy","issn_l":"1525-0016","issn":["1525-0016","1525-0024"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-1","poland-140","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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Therapy","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1016/s1525-0016(16)33941-7","doi":"https://doi.org/10.1016/s1525-0016(16)33941-7","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s1525-0016(16)33941-7","pdf_url":"http://www.cell.com/article/S1525001616339417/pdf","source":{"id":"https://openalex.org/S51596929","display_name":"Molecular Therapy","issn_l":"1525-0016","issn":["1525-0016","1525-0024"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-1","poland-140","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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Therapy","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9763000011444092}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":false},"content_urls":{"pdf":"https://content.openalex.org/works/W2563250258.pdf"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4398785258","https://openalex.org/W2565679237","https://openalex.org/W2974703082","https://openalex.org/W2023456870","https://openalex.org/W1700608924","https://openalex.org/W4389220212","https://openalex.org/W2078458905","https://openalex.org/W1234938885","https://openalex.org/W611184105","https://openalex.org/W2939213312"],"abstract_inverted_index":{"Chronic":[0],"granulomatous":[1,35],"disease":[2,36],"is":[3,291],"an":[4],"immune":[5],"deficiency":[6,26],"caused":[7],"by":[8,153,190,264,278],"defective":[9],"phagocyte":[10],"NADPH":[11],"oxidase":[12,276],"resulting":[13,23,49],"in":[14,24,46,50,79,85,225,293,300],"severe":[15],"infections":[16],"and":[17,38,56,84,139,179,205,340],"autoimmune":[18],"complications.":[19],"NCF1":[20,68,77,124,213],"gene":[21,69,161,188,208,270,326],"mutations":[22,344],"p47phox":[25,59,288],"are":[27],"the":[28,76,96,122,128,134,137,149,164,310,347],"most":[29,150],"common":[30],"cause":[31],"of":[32,41,58,103,108,136,148,210,223,234,275,307,338],"autosomal-recessive":[33],"chronic":[34],"(AR-CGD),":[37],"notably,":[39],">80%":[40,248],"patients":[42],"have":[43],"homozygous":[44],"GT-deletions":[45],"exon":[47,104,115,125,131],"2,":[48],"a":[51,109,155,182,185,329],"frame":[52],"shift,":[53],"premature":[54],"termination,":[55],"absence":[57],"expression.":[60],"Here":[61],"we":[62,315],"show":[63,316],"two":[64,168],"nucleofection":[65],"strategies":[66,259],"for":[67,160,195,256,334,343],"correction":[70,209,224,258,274,332,342],"using":[71,163],"zinc-finger":[72],"nuclease":[73],"(ZFN)":[74],"targeting":[75],"locus":[78],"patient":[80,200,322],"EBV-immortalized":[81,201],"B":[82,202,254],"cells":[83,89,255,323],"induced":[86],"pluripotent":[87],"stem":[88],"(iPSC)":[90],"derived":[91],"from":[92,121,218,269,296,320],"p47phox-deficient":[93],"patients.":[94],"With":[95,285],"first":[97],"strategy,":[98],"ZFN-mediated":[99],"cut":[100],"at":[101,309],"start":[102],"2":[105,132],"allows":[106],"insertion":[107,245],"minigene":[110,130,204,341],"(NCF1":[111],"cDNA":[112,138],"with":[113],"deleted":[114],"1)":[116],"to":[117,127,173,193,237,242,247],"allow":[118,194],"continuous":[119],"transcription":[120],"endogenous":[123],"1":[126],"donor":[129,158,241],"until":[133],"end":[135],"beta-globin":[140],"polyadenylation":[141],"signal.":[142],"The":[143,167,221],"second":[144],"strategy":[145],"takes":[146],"advantage":[147],"prevalent":[151],"GT-deletion":[152],"providing":[154],"dinucleotide":[156,206,239,331],"corrective":[157,240],"plasmid":[159],"editing":[162],"same":[165],"ZFNs.":[166],"donors":[169],"contain":[170],"~750":[171],"bp":[172,175],"1000":[174],"flanking":[176],"homology":[177],"arms":[178],"also":[180],"encode":[181],"selectable":[183],"marker:":[184],"puromycin":[186,250],"resistance":[187],"flanked":[189],"loxP":[191],"sites":[192],"excision":[196],"after":[197,216,249],"selection.":[198,251],"In":[199,313],"cells,":[203],"targeted":[207,330],"constitutively":[211],"active":[212],"was":[214],"8-20%":[215],"puromycin-selection":[217],"obtained":[219],"clones.":[220],"rates":[222],"iPSC":[226,243,297,318],"were":[227],"generally":[228],"lower,":[229],"less":[230],"than":[231,336,346],"2%.":[232],"Use":[233],"AAV2":[235],"vector":[236],"deliver":[238],"increased":[244],"efficiency":[246],"Gene":[252],"corrected":[253,271,311,327],"both":[257,286],"restored":[260],"ROS":[261],"function,":[262],"shown":[263],"chemiluminescence":[265,279],"assay.":[266,284],"Neutrophils":[267],"differentiated":[268,295],"iPSCs":[272],"demonstrated":[273],"activity":[277],"or":[280],"dihydrorhodamine":[281],"flow":[282],"cytometry":[283],"methods,":[287],"protein":[289],"expression":[290,308],"seen":[292],"neutrophils":[294],"but":[298],"not":[299],"undifferentiated":[301],"iPSC,":[302],"demonstrating":[303],"cell":[304],"type-specific":[305],"regulation":[306],"locus.":[312],"summary,":[314],"that":[317],"generated":[319],"CGD":[321],"can":[324],"be":[325],"through":[328],"method":[333],"greater":[335],"80%":[337],"alleles":[339],"other":[345],"GT-deletions.":[348]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2017-01-06T00:00:00"}