{"id":"https://openalex.org/W2971752154","doi":"https://doi.org/10.1093/hmg/ddz182","title":"Gene therapy matures to medicines","display_name":"Gene therapy matures to medicines","publication_year":2019,"publication_date":"2019-08-28","ids":{"openalex":"https://openalex.org/W2971752154","doi":"https://doi.org/10.1093/hmg/ddz182","mag":"2971752154","pmid":"https://pubmed.ncbi.nlm.nih.gov/31595292"},"language":"en","primary_location":{"id":"doi:10.1093/hmg/ddz182","doi":"https://doi.org/10.1093/hmg/ddz182","is_oa":true,"landing_page_url":"https://doi.org/10.1093/hmg/ddz182","pdf_url":"https://academic.oup.com/hmg/article-pdf/28/R1/R1/30160352/ddz182.pdf","source":{"id":"https://openalex.org/S166515463","display_name":"Human Molecular Genetics","issn_l":"0964-6906","issn":["0964-6906","1460-2083"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Human Molecular Genetics","raw_type":"journal-article"},"volume":null,"type":"editorial","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://academic.oup.com/hmg/article-pdf/28/R1/R1/30160352/ddz182.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5045163747","display_name":"Beverly L. Davidson","orcid":"https://orcid.org/0000-0002-3715-6290","observed_orcids":["https://orcid.org/0000-0002-3715-6290"]},"institutions":[{"id":"https://openalex.org/I1335321130","display_name":"Children's Hospital of Philadelphia","ror":"https://ror.org/01z7r7q48","country_code":"US","type":"funder","lineage":["https://openalex.org/I1335321130"]},{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Beverly L Davidson","raw_affiliation_strings":["The Department of Pathology and Laboratory Medicine Perelman School at the University of Pennsylvania","The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, the Children's Hospital of Philadelphia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Department of Pathology and Laboratory Medicine Perelman School at the University of Pennsylvania","institution_ids":["https://openalex.org/I79576946"]},{"raw_affiliation_string":"The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, the Children's Hospital of Philadelphia","institution_ids":["https://openalex.org/I1335321130"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5083658192","display_name":"Valder R. Arruda","orcid":"https://orcid.org/0000-0002-8100-5481","observed_orcids":["https://orcid.org/0000-0002-8100-5481"]},"institutions":[{"id":"https://openalex.org/I1335321130","display_name":"Children's Hospital of Philadelphia","ror":"https://ror.org/01z7r7q48","country_code":"US","type":"funder","lineage":["https://openalex.org/I1335321130"]},{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Valder R Arruda","raw_affiliation_strings":["The Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA USA","The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, the Children's Hospital of Philadelphia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA USA","institution_ids":["https://openalex.org/I79576946"]},{"raw_affiliation_string":"The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, the Children's Hospital of Philadelphia","institution_ids":["https://openalex.org/I1335321130"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5045163747","https://openalex.org/A5083658192"],"corresponding_institution_ids":["https://openalex.org/I1335321130","https://openalex.org/I79576946"],"apc_list":{"value":4390,"currency":"USD","value_usd":4390},"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"28","issue":"R1","first_page":"R1","last_page":"R2"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10613","display_name":"Virus-based gene therapy research","score":0.9951000213623047,"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"}},"topics":[{"id":"https://openalex.org/T10613","display_name":"Virus-based gene therapy research","score":0.9951000213623047,"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/T10725","display_name":"RNA Interference and Gene Delivery","score":0.0019000000320374966,"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/T10878","display_name":"CRISPR and Genetic Engineering","score":0.0008999999845400453,"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/gene-therapy","display_name":"gene therapy","score":0.9729999899864197},{"id":"https://openalex.org/keywords/regulatory-approval","display_name":"regulatory approval","score":0.5730000138282776},{"id":"https://openalex.org/keywords/rpe65","display_name":"RPE65","score":0.8679999709129333},{"id":"https://openalex.org/keywords/spinal-muscular-atrophy-type-1","display_name":"spinal muscular atrophy type 1","score":0.9039999842643738},{"id":"https://openalex.org/keywords/lipoprotein-lipase-deficiency","display_name":"lipoprotein lipase deficiency","score":0.9900000095367432},{"id":"https://openalex.org/keywords/lentiviral-vectors","display_name":"lentiviral vectors","score":0.8080000281333923},{"id":"https://openalex.org/keywords/viral-vectors","display_name":"viral vectors","score":0.4749999940395355},{"id":"https://openalex.org/keywords/non-viral-vectors","display_name":"non-viral vectors","score":0.6850000023841858},{"id":"https://openalex.org/keywords/chimeric-antigen-receptor-t-cells","display_name":"chimeric antigen receptor T cells","score":0.7879999876022339},{"id":"https://openalex.org/keywords/factor-ix","display_name":"factor IX","score":0.34599998593330383},{"id":"https://openalex.org/keywords/hemophilia-b","display_name":"hemophilia B","score":0.9190000295639038},{"id":"https://openalex.org/keywords/primary-immunodeficiency","display_name":"primary immunodeficiency","score":0.527999997138977}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.9004954099655151},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.504308819770813},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.48407235741615295},{"id":"https://openalex.org/C111599444","wikidata":"https://www.wikidata.org/wiki/Q213901","display_name":"Genetic enhancement","level":3,"score":0.4407910704612732},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.42235666513442993}],"mesh":[{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015316","descriptor_name":"Genetic Therapy","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D015316","descriptor_name":"Genetic Therapy","qualifier_ui":"Q000639","qualifier_name":"trends","is_major_topic":true},{"descriptor_ui":"D062346","descriptor_name":"Molecular Medicine","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D062346","descriptor_name":"Molecular Medicine","qualifier_ui":"Q000639","qualifier_name":"trends","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1093/hmg/ddz182","doi":"https://doi.org/10.1093/hmg/ddz182","is_oa":true,"landing_page_url":"https://doi.org/10.1093/hmg/ddz182","pdf_url":"https://academic.oup.com/hmg/article-pdf/28/R1/R1/30160352/ddz182.pdf","source":{"id":"https://openalex.org/S166515463","display_name":"Human Molecular Genetics","issn_l":"0964-6906","issn":["0964-6906","1460-2083"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Human Molecular Genetics","raw_type":"journal-article"},{"id":"pmid:31595292","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/31595292","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":"Human molecular genetics","raw_type":"Editorial"}],"best_oa_location":{"id":"doi:10.1093/hmg/ddz182","doi":"https://doi.org/10.1093/hmg/ddz182","is_oa":true,"landing_page_url":"https://doi.org/10.1093/hmg/ddz182","pdf_url":"https://academic.oup.com/hmg/article-pdf/28/R1/R1/30160352/ddz182.pdf","source":{"id":"https://openalex.org/S166515463","display_name":"Human Molecular Genetics","issn_l":"0964-6906","issn":["0964-6906","1460-2083"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Human Molecular Genetics","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9763000011444092,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"display_name":"Zero hunger","score":0.6399999856948853,"id":"https://metadata.un.org/sdg/2"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G9000894743","display_name":"Hemostasis and Thrombosis: Chemistry, Biology and Physiology","funder_award_id":"P01HL139420","funder_id":"https://openalex.org/F4320337338","funder_display_name":"National Heart, Lung, and Blood Institute"}],"funders":[{"id":"https://openalex.org/F4320337338","display_name":"National Heart, Lung, and Blood Institute","ror":"https://ror.org/012pb6c26"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2971752154.pdf","grobid_xml":"https://content.openalex.org/works/W2971752154.grobid-xml"},"referenced_works_count":2,"referenced_works":["https://openalex.org/W2154123437","https://openalex.org/W2308015421"],"related_works":["https://openalex.org/W3124666661","https://openalex.org/W2308015421","https://openalex.org/W2782917400","https://openalex.org/W3105402850","https://openalex.org/W2969783143","https://openalex.org/W4386593133","https://openalex.org/W2997125990","https://openalex.org/W4413971609","https://openalex.org/W2794507700","https://openalex.org/W3144545288"],"abstract_inverted_index":{"Three":[0],"years":[1,682],"ago,":[2],"Human":[3],"Molecular":[4],"Genetics":[5],"commissioned":[6],"a":[7,38,95,109,120,393,563,571,625,714],"compendium":[8],"on":[9,55],"gene":[10,107,209,253,330,404,461,472,483,517,545,577,703],"therapy":[11,175,210,254,462,546,578,704],"approaches":[12,211],"and":[13,25,30,66,82,119,142,215,233,245,273,293,335,369,458,486,511,525,559,634,692],"advances":[14,463,481,701],"(1).":[15],"At":[16],"that":[17,44,228,304,381,498,508,539,598,628,705],"time,":[18],"we":[19,51,199,221,583,629,642,684],"had":[20],"already":[21],"witnessed":[22],"substantial":[23],"growth":[24],"development":[26,492],"in":[27,32,46,54,105,205,251,265,291,364,471,482,589,639,669,702],"the":[28,33,42,78,106,125,169,186,226,235,252,257,266,299,307,333,345,352,370,377,400,403,416,438,450,478,513,585,591,594,649,662,672,678,710],"field":[29,255,552],"were":[31,52],"midst":[34],"of":[35,139,243,322,329,337,347,373,379,402,452,480,493,502,505,516,565,568,587,597,624,664,675,713],"human":[36],"trials,":[37],"solid":[39],"advance":[40],"from":[41,203,709],"stage":[43,170],"existed":[45],"2011":[47],"(2).":[48],"In":[49,133,196,677],"2016":[50],"closing":[53],"possible":[56],"approvals":[57],"for":[58,91,131,164,171,184,192,230,237,301,309,326,384,392,420,427,449,543,548],"genetic":[59,277],"reagents":[60],"that,":[61],"when":[62,631,648],"delivered,":[63],"would":[64],"dramatically":[65],"positively":[67],"affect":[68],"people\u2019s":[69],"lives.":[70],"Today,":[71],"there":[72],"are":[73,212,222,319,340,464],"drugs":[74],"approved":[75,89],"by":[76,101,249,270,343,469],"both":[77],"Federal":[79],"Drug":[80],"Administration":[81],"European":[83],"Medicines":[84],"Agency.":[85],"Regulatory":[86],"agencies":[87],"have":[88,145,200,570,584,605,643,687,707],"treatments":[90],"inherited":[92,97,143,276],"disorders":[93,281],"including":[94],"rare":[96],"retinal":[98],"dystrophy":[99],"(caused":[100],"autosomal":[102],"recessive":[103],"mutations":[104],"RPE65),":[108],"motor":[110],"neuron":[111],"disease":[112,457],"(spinal":[113],"muscular":[114],"atrophy":[115],"type":[116,174],"1,":[117],"SMA-1)":[118],"lipoprotein":[121],"lipase":[122],"deficiency,":[123],"although":[124],"latter":[126],"is":[127,261,408,446,651],"no":[128],"longer":[129],"available":[130],"use.":[132],"addition,":[134],"lentiviral-mediated":[135],"ex":[136],"vivo":[137,365],"correction":[138],"primary":[140],"immunodeficiencies":[141],"hemoglobinopathies":[144],"been":[146,190,287,606],"approved.":[147],"For":[148,313,357,489],"acquired":[149,280],"disorders,":[150],"T":[151],"cells":[152],"modified":[153],"to":[154,194,223,350,437,534,555,562,600,619,637,653,656,658,686,693,696],"express":[155],"chimeric":[156],"antigen":[157],"receptors":[158],"(CAR-T":[159],"cells)":[160],"received":[161],"regulatory":[162,324],"approval":[163],"B":[165,429,521],"cell":[166,338,397,456],"malignancies,":[167],"setting":[168],"similar":[172],"CAR-T":[173],"development.":[176],"While":[177],"individually":[178],"each":[179],"drug":[180],"required":[181,419],"enormous":[182],"effort":[183],"approval,":[185],"path":[187],"has":[188,286,432],"now":[189],"paved":[191],"others":[193],"follow.":[195],"this":[197],"issue,":[198],"compiled":[201],"reviews":[202,218],"experts":[204],"various":[206],"fields":[207],"where":[208,220],"being":[213,341,406,447,465],"developed":[214],"refined.":[216],"These":[217,529],"outline":[219],"date,":[224],"explain":[225],"barriers":[227],"remain":[229],"specific":[231,495],"indications":[232],"discuss":[234],"roadmap":[236],"future":[238],"advances.":[239],"The":[240,551,576],"hard":[241],"work":[242],"careful":[244],"thoughtful":[246],"scientific":[247],"studies":[248],"many":[250],"over":[256],"past":[258],"several":[259],"decades":[260],"finally":[262],"bearing":[263],"fruit\u2014measured":[264],"profound":[267],"improvements":[268,470],"experienced":[269],"patients,":[271],"young":[272],"aged,":[274],"with":[275,454,537,608,698],"diseases":[278],"or":[279,389,396,504,593,614,646,668],"such":[282],"as":[283,296,298,413],"cancer.":[284],"There":[285],"recent":[288],"important":[289,410,690],"progress":[290],"viral":[292],"non-viral":[294],"vectors,":[295],"well":[297],"technologies":[300,485],"continued":[302,371],"advancements":[303],"could":[305],"open":[306],"door":[308],"new":[310,374,557,622],"translational":[311],"applications.":[312],"lentivirus":[314],"vectors":[315,359,558],"transgene":[316],"expression":[317,560],"cassettes":[318,561],"taking":[320],"advantage":[321],"host-cell":[323],"factors":[325],"enhanced":[327],"control":[328],"expression.":[331],"And,":[332],"scope":[334],"efficiency":[336],"targeting":[339],"improved":[342,544,607],"expanding":[344],"variety":[346],"envelopes":[348],"used":[349,448,618],"pseudotype":[351],"virion":[353],"during":[354],"vector":[355,417],"production.":[356],"encapsidated":[358],"like":[360],"recombinant":[361],"adenoassociated":[362],"viruses,":[363],"evolution,":[366],"capsid":[367],"shuffling":[368],"discovery":[372],"serotypes":[375],"deepen":[376],"toolbox":[378],"virions":[380],"can":[382,540],"provide":[383],"transduction":[385],"at":[386],"lower":[387,500],"doses":[388,418,501],"greater":[390],"specificity":[391],"given":[394],"tissue":[395],"type.":[398],"Improving":[399],"activity":[401,435,496],"product":[405],"expressed":[407],"another":[409],"step":[411],"forward,":[412],"it":[414],"lowers":[415],"efficacy.":[421],"Indeed,":[422],"factor":[423],"IX":[424],"(FIX)":[425],"Padua":[426],"hemophilia":[428],"(FIX":[430],"deficiency)":[431],"8-fold":[433],"increased":[434],"compared":[436],"wild-type":[439],"protein.":[440],"Similarly,":[441],"an":[442],"anti-sickling":[443],"hemoglobin":[444],"variant":[445],"treatment":[451,638],"patients":[453,633],"sickle":[455],"thalassemia.":[459],"Thus":[460],"extended":[466],"not":[467,652],"only":[468],"delivery":[473,518],"technology":[474],"but":[475,655],"also":[476],"through":[477,491],"use":[479],"editing":[484],"protein":[487],"engineering.":[488],"example,":[490],"higher":[494],"molecules":[497],"allow":[499],"vector,":[503],"truncated":[506],"proteins":[507],"preserve":[509],"function":[510],"fit":[512],"packaging":[514],"limitations":[515],"vehicles":[519],"(e.g.":[520],"domain-deleted":[522],"FVIII;":[523],"microdystrophins":[524],"alternative":[526],"CRISPR":[527],"systems).":[528],"discoveries":[530],"should":[531,580],"encourage":[532],"researchers":[533],"identify":[535],"variants":[536],"characteristics":[538],"be":[541,617,694],"harnessed":[542],"dosing":[547],"additional":[549,700],"disorders.":[550],"will":[553,706],"continue":[554],"apply":[556],"myriad":[564],"diseases,":[566],"some":[567,659,681],"which":[569],"poorly":[572],"defined":[573,660],"natural":[574],"history.":[575],"community":[579],"question":[581],"whether":[582],"depth":[586],"experience":[588],"understanding":[590],"variance,":[592,599],"root":[595],"cause":[596],"know":[601],"if":[602],"clinical":[603,626,673],"outcomes":[604],"treatment.":[609],"Can":[610],"artificial":[611],"intelligence":[612],"algorithms":[613],"machine":[615],"learning":[616],"help":[620],"unravel":[621],"features":[623],"course":[627,674],"miss":[630],"considering":[632],"their":[635],"responses":[636],"isolation?":[640],"Should":[641],"different":[644],"criteria":[645],"motivations":[647],"goal":[650],"cure,":[654],"improve":[657],"degree,":[661],"quality":[663],"life":[665],"rather":[666],"than,":[667],"addition":[670],"to,":[671],"disease?":[676],"next":[679],"compendium,":[680],"ahead,":[683],"hope":[685],"addressed":[688],"these":[689],"questions":[691],"able":[695],"share":[697],"you":[699],"emerged":[708],"collective":[711],"creativity":[712],"re-energized":[715],"field.":[716]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2019-09-12T00:00:00"}