{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:55:01Z","timestamp":1790826901481,"version":"4.1.0"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","award":["FA1-00613"],"award-info":[{"award-number":["FA1-00613"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008623","name":"Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008623","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007185","name":"University of California, Los Angeles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI074043"],"award-info":[{"award-number":["R01-AI074043"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01-HL073104"],"award-info":[{"award-number":["P01-HL073104"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50-HL54850"],"award-info":[{"award-number":["P50-HL54850"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Methods & Clinical Development"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.omtm.2021.02.007","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T01:11:26Z","timestamp":1613437886000},"page":"765-778","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Gene delivery using AAV8 in\u00a0vivo for disease stabilization in a bimodal gene therapy approach for the treatment of ADA-deficient SCID"],"prefix":"10.1016","volume":"20","author":[{"given":"Denise A.","family":"Carbonaro-Sarracino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle N.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald B.","family":"Kohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2021.02.007_bib1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1006\/cimm.1993.1299","article-title":"Severe combined immunodeficiency of reduced severity due to homozygosity for an adenosine deaminase missense mutation (Arg253Pro)","volume":"152","author":"Hirschhorn","year":"1993","journal-title":"Cell. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib2","first-page":"291","article-title":"Adenosine deaminase deficiency: clinical expression, molecular basis, and therapy","volume":"35","author":"Hershfield","year":"1998","journal-title":"Semin. Hematol."},{"key":"10.1016\/j.omtm.2021.02.007_bib3","first-page":"491","article-title":"Heterogeneity of biochemical, clinical and immunological parameters in severe combined immunodeficiency due to adenosine deaminase deficiency","volume":"70","author":"Morgan","year":"1987","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib4","doi-asserted-by":"crossref","first-page":"S228","DOI":"10.1016\/S0090-1229(95)90306-2","article-title":"PEG-ADA replacement therapy for adenosine deaminase deficiency: an update after 8.5 years","volume":"76","author":"Hershfield","year":"1995","journal-title":"Clin. Immunol. Immunopathol."},{"key":"10.1016\/j.omtm.2021.02.007_bib5","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.jaci.2018.08.024","article-title":"Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency","volume":"143","author":"Kohn","year":"2019","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib6","first-page":"349","article-title":"Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID)","volume":"3","author":"Booth","year":"2009","journal-title":"Biologics"},{"key":"10.1016\/j.omtm.2021.02.007_bib7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.clim.2005.07.006","article-title":"Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID)","volume":"117","author":"Chan","year":"2005","journal-title":"Clin. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib8","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1182\/blood-2011-12-396879","article-title":"Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency","volume":"120","author":"Hassan","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11882-016-0615-8","article-title":"Gene Therapy for the Treatment of Primary Immune Deficiencies","volume":"16","author":"Kuo","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"key":"10.1016\/j.omtm.2021.02.007_bib10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1182\/blood-2016-01-688226","article-title":"Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency","volume":"128","author":"Cicalese","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib11","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1182\/blood-2012-02-408591","article-title":"Gene therapy\/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction","volume":"120","author":"Carbonaro","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib12","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1073\/pnas.92.9.3673","article-title":"Disruption of the adenosine deaminase gene causes hepatocellular impairment and perinatal lethality in mice","volume":"92","author":"Wakamiya","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2021.02.007_bib13","doi-asserted-by":"crossref","first-page":"23891","DOI":"10.1074\/jbc.270.41.23891","article-title":"Tissue-specific rescue suggests that placental adenosine deaminase is important for fetal development in mice","volume":"270","author":"Blackburn","year":"1995","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.omtm.2021.02.007_bib14","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/ng0795-279","article-title":"Adenosine-deaminase-deficient mice die perinatally and exhibit liver-cell degeneration, atelectasis and small intestinal cell death","volume":"10","author":"Migchielsen","year":"1995","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2021.02.007_bib15","doi-asserted-by":"crossref","first-page":"5093","DOI":"10.1074\/jbc.273.9.5093","article-title":"Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency","volume":"273","author":"Blackburn","year":"1998","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.omtm.2021.02.007_bib16","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1038\/mt.2014.88","article-title":"Effects of vector backbone and pseudotype on lentiviral vector-mediated gene transfer: studies in infant ADA-deficient mice and rhesus monkeys","volume":"22","author":"Carbonaro Sarracino","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib17","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/mt.2008.72","article-title":"Gene delivery to the juvenile mouse liver using AAV2\/8 vectors","volume":"16","author":"Cunningham","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/mt.2013.265","article-title":"Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency","volume":"22","author":"Carbonaro","year":"2014","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib19","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1089\/hum.2010.121","article-title":"Recombinant adeno-associated virus-mediated gene transfer for the potential therapy of adenosine deaminase-deficient severe combined immune deficiency","volume":"22","author":"Silver","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib20","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s10875-017-0433-3","article-title":"Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations","volume":"37","author":"Bradford","year":"2017","journal-title":"J.\u00a0Clin. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib21","doi-asserted-by":"crossref","first-page":"32114","DOI":"10.1074\/jbc.M005153200","article-title":"The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities","volume":"275","author":"Blackburn","year":"2000","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.omtm.2021.02.007_bib22","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.ymthe.2006.02.013","article-title":"In\u00a0vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice: a novel form of enzyme replacement therapy for ADA deficiency","volume":"13","author":"Carbonaro","year":"2006","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nbt1073","article-title":"Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart","volume":"23","author":"Wang","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2021.02.007_bib24","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1038\/mt.2010.175","article-title":"Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy","volume":"18","author":"Hurlbut","year":"2010","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib25","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10875-012-9658-3","article-title":"Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency","volume":"32","author":"Booth","year":"2012","journal-title":"J.\u00a0Clin. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib26","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.jaci.2012.02.003","article-title":"Pulmonary alveolar proteinosis in patients with adenosine deaminase deficiency","volume":"129","author":"Grunebaum","year":"2012","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.omtm.2021.02.007_bib27","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1182\/blood-2008-04-151332","article-title":"Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies","volume":"112","author":"Titman","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib28","doi-asserted-by":"crossref","first-page":"3524","DOI":"10.1182\/blood-2009-06-189209","article-title":"How I treat ADA deficiency","volume":"114","author":"Gaspar","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib29","doi-asserted-by":"crossref","first-page":"40136","DOI":"10.1038\/srep40136","article-title":"Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients","volume":"7","author":"Sauer","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2021.02.007_bib30","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/hmg\/ddq514","article-title":"Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice","volume":"20","author":"Dominguez","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2021.02.007_bib31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nbt.1515","article-title":"Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes","volume":"27","author":"Foust","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2021.02.007_bib32","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.omtm.2019.11.004","article-title":"Dosing and Re-Administration of Lentiviral Vector for In\u00a0Vivo Gene Therapy in Rhesus Monkeys and ADA-Deficient Mice","volume":"16","author":"Carbonaro-Sarracino","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2021.02.007_bib33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.omtm.2017.11.007","article-title":"Emerging Issues in AAV-Mediated In\u00a0Vivo Gene Therapy","volume":"8","author":"Colella","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2021.02.007_bib34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41587-020-0741-7","article-title":"A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells","volume":"39","author":"Nguyen","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2021.02.007_bib35","doi-asserted-by":"crossref","first-page":"5745","DOI":"10.1182\/blood-2007-08-103663","article-title":"Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion","volume":"111","author":"Carbonaro","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib36","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1242\/dev.124.16.3089","article-title":"Genetically engineered mice demonstrate that adenosine deaminase is essential for early postimplantation development","volume":"124","author":"Blackburn","year":"1997","journal-title":"Development"},{"key":"10.1016\/j.omtm.2021.02.007_bib37","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1182\/blood.V94.10.3349.422k05_3349_3357","article-title":"Improved expression in hematopoietic and lymphoid cells in mice after transplantation of bone marrow transduced with a modified retroviral vector","volume":"94","author":"Halene","year":"1999","journal-title":"Blood"},{"key":"10.1016\/j.omtm.2021.02.007_bib38","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/mt.2008.5","article-title":"Physiological promoters reduce the genotoxic risk of integrating gene vectors","volume":"16","author":"Zychlinski","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2021.02.007_bib39","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1128\/JVI.72.12.9873-9880.1998","article-title":"Self-inactivating lentivirus vector for safe and efficient in\u00a0vivo gene delivery","volume":"72","author":"Zufferey","year":"1998","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.omtm.2021.02.007_bib40","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.283.5402.682","article-title":"Transduction of human CD34+ cells that mediate long-term engraftment of NOD\/SCID mice by HIV vectors","volume":"283","author":"Miyoshi","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.omtm.2021.02.007_bib41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jviromet.2011.06.019","article-title":"Highly efficient large-scale lentiviral vector concentration by tandem tangential flow filtration","volume":"177","author":"Cooper","year":"2011","journal-title":"J.\u00a0Virol. Methods"},{"key":"10.1016\/j.omtm.2021.02.007_bib42","series-title":"SAS\/STAT User\u2019s Guide, Version 9.3","year":"2012"}],"container-title":["Molecular Therapy - Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S232905012100022X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S232905012100022X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:52:54Z","timestamp":1778867574000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S232905012100022X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":42,"alternative-id":["S232905012100022X"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2021.02.007","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gene delivery using AAV8 in\u00a0vivo for disease stabilization in a bimodal gene therapy approach for the treatment of ADA-deficient SCID","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2021.02.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors.","name":"copyright","label":"Copyright"}]}}