{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:56:08Z","timestamp":1777895768829,"version":"3.51.4"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","pediatr-neonatol.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics & Neonatology"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1016\/j.pedneo.2022.09.004","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T12:49:54Z","timestamp":1664542194000},"page":"S3-S9","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"S1","title":["Adeno-associated virus vector-based gene therapies for pediatric diseases"],"prefix":"10.1016","volume":"64","author":[{"given":"Kazuhiro","family":"Muramatsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichi","family":"Muramatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.pedneo.2022.09.004_bib1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.175.4025.949","article-title":"Gene therapy for human genetic disease?","volume":"175","author":"Friedmann","year":"1972","journal-title":"Science"},{"key":"10.1016\/j.pedneo.2022.09.004_bib2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-021-00487-6","article-title":"Viral vector platforms within the gene therapy landscape","volume":"6","author":"Bulcha","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib3","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/s41467-022-28762-2","article-title":"A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders","volume":"13","author":"Tucci","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.pedneo.2022.09.004_bib4","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1007\/s10072-021-05412-x","article-title":"New disease-modifying therapies for two genetic childhood-onset neurometabolic disorders (metachromatic leucodystrophy and adrenoleucodystrophy)","volume":"42","author":"Federico","year":"2021","journal-title":"Neurol Sci"},{"key":"10.1016\/j.pedneo.2022.09.004_bib5","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.pedneo.2022.09.004_bib6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1089\/humc.2017.010","article-title":"Persistent expression of dopamine-synthesizing enzymes 15 Years after gene transfer in a primate model of Parkinson\u2019s disease","volume":"28","author":"Sehara","year":"2017","journal-title":"Hum Gene Ther Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1128\/JVI.79.1.214-224.2005","article-title":"Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice","volume":"79","author":"Nakai","year":"2005","journal-title":"J Virol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib8","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.pedneo.2022.09.004_bib9","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1089\/hum.2021.169","article-title":"Capsid-engineering for central nervous system-directed gene therapy with adeno-associated virus vectors","volume":"32","author":"Macdonald","year":"2021","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ymthe.2021.11.005","article-title":"Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency","volume":"30","author":"Tai","year":"2022","journal-title":"Mol Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/brain\/awy331","article-title":"Gene therapy improves motor and mental function of aromatic l-amino acid decarboxylase deficiency","volume":"142","author":"Kojima","year":"2019","journal-title":"Brain"},{"key":"10.1016\/j.pedneo.2022.09.004_bib12","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1038\/s41467-021-24524-8","article-title":"Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons","volume":"12","author":"Pearson","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.pedneo.2022.09.004_bib13","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202114712","article-title":"Gene therapy in the putamen for curing AADC deficiency and Parkinson\u2019s disease","volume":"13","author":"Hwu","year":"2021","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1089\/10430340252792486","article-title":"Behavioral recovery in a primate model of Parkinson\u2019s disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes","volume":"13","author":"Muramatsu","year":"2002","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib15","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-dose gene-replacement therapy for spinal muscular atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib16","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s41591-022-01866-4","article-title":"Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial","volume":"28","author":"Strauss","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib17","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/s41591-022-01867-3","article-title":"Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial","volume":"28","author":"Strauss","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib18","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.molmed.2021.03.010","article-title":"Adeno-associated virus vector for central nervous system gene therapy","volume":"27","author":"Zhu","year":"2021","journal-title":"Trends Mol Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib19","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1089\/hum.2008.022","article-title":"Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA","volume":"19","author":"Worgall","year":"2008","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib20","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1089\/hum.2020.038","article-title":"Gene therapy targeting the inner retina rescues the retinal phenotype in a mouse model of CLN3 Batten disease","volume":"31","author":"Kleine Holthaus","year":"2020","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib21","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.omtm.2022.04.010","article-title":"Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler","volume":"25","author":"Jin","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib22","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.ymthe.2020.03.018","article-title":"A highly efficacious PS gene editing system corrects metabolic and neurological complications of mucopolysaccharidosis type I","volume":"28","author":"Ou","year":"2020","journal-title":"Mol Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib23","first-page":"S68","article-title":"EMPOWERS: a phase 1\/2 clinical trial of SB-318 ZFN-mediated in vivo human genome editing for treatment of MPS I (Hurler syndrome)","volume":"126","author":"Harmatz","year":"2019","journal-title":"Mol Genet Metabol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib24","first-page":"S104","article-title":"CHAMPIONS: a phase 1\/2 clinical trial with dose escalation of SB-913 ZFN-mediated in vivo human genome editing for treatment of MPS II (Hunter syndrome)","volume":"126","author":"Muenzer","year":"2019","journal-title":"Mol Genet Metabol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib25","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa2106596","article-title":"Hematopoietic stem- and progenitor-cell gene therapy for Hurler syndrome","volume":"385","author":"Gentner","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib26","article-title":"A novel preclinical model of mucopolysaccharidosis type II for developing human hematopoietic stem cell gene therapy","author":"Shimada","year":"2022","journal-title":"Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib27","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1089\/hum.2020.175","article-title":"Gene therapy in a mouse model of Niemann-pick disease type C1","volume":"32","author":"Kurokawa","year":"2021","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib28","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1001\/jamaneurol.2020.1484","article-title":"Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a Nonrandomized controlled trial","volume":"77","author":"Mendell","year":"2020","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib29","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41587-022-01346-7","article-title":"Gene therapy at the crossroads","volume":"40","year":"2022","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib30","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1089\/hum.2022.29211.bfs","article-title":"Food and drug administration lifts clinical Hold on pfizer Duchenne muscular dystrophy gene therapy linked to patient death","volume":"33","author":"Philippidis","year":"2022","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib31","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1089\/hum.2021.29182.bfs","article-title":"Fourth boy dies in clinical trial of Astellas\u2019 AT132","volume":"32","author":"Philippidis","year":"2021","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib32","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.omtm.2022.01.007","article-title":"Prednisolone reduces the interferon response to AAV in cynomolgus macaques and may increase liver gene expression","volume":"24","author":"Wang","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib33","doi-asserted-by":"crossref","first-page":"9322","DOI":"10.1038\/s41598-021-88614-9","article-title":"Engineered adeno-associated virus 3 vector with reduced reactivity to serum antibodies","volume":"11","author":"Ito","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.pedneo.2022.09.004_bib34","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41591-022-01751-0","article-title":"Interindividual variability in transgene mRNA and protein production following adeno-associated virus gene therapy for hemophilia A","volume":"28","author":"Fong","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib35","doi-asserted-by":"crossref","first-page":"e504","DOI":"10.1016\/S2352-3026(22)00113-2","article-title":"Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial","volume":"9","author":"Xue","year":"2022","journal-title":"Lancet Haematol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib36","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1038\/s41598-017-04625-5","article-title":"CRISPR\/Cas9-mediated genome editing via postnatal administration of AAV vector cures haemophilia B mice","volume":"7","author":"Ohmori","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.pedneo.2022.09.004_bib37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.15252\/emmm.201404392","article-title":"HMGB1 facilitates repair of mitochondrial DNA damage and extends the lifespan of mutant ataxin-1 knock-in mice","volume":"7","author":"Ito","year":"2015","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib38","doi-asserted-by":"crossref","first-page":"347ra94","DOI":"10.1126\/scitranslmed.aaf5660","article-title":"An miRNA-mediated therapy for SCA6 blocks IRES-driven translation of the CACNA1A second cistron","volume":"8","author":"Miyazaki","year":"2016","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2022.868531","article-title":"Gene and cell therapy for epilepsy: a mini review","volume":"15","author":"Shaimardanova","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"10.1016\/j.pedneo.2022.09.004_bib40","doi-asserted-by":"crossref","DOI":"10.1002\/jgm.3402","article-title":"Global brain delivery of neuroligin 2 gene ameliorates seizures in a mouse model of epilepsy","volume":"24","author":"Oguro","year":"2022","journal-title":"J Gene Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib41","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1089\/hum.2019.225","article-title":"Sexually divergent mortality and partial phenotypic rescue after gene therapy in a mouse model of dravet syndrome","volume":"31","author":"Niibori","year":"2020","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib42","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ymthe.2019.08.018","article-title":"dCas9-Based Scn1a gene activation restores inhibitory interneuron excitability and Attenuates seizures in Dravet syndrome mice","volume":"28","author":"Colasante","year":"2020","journal-title":"Mol Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.104954","article-title":"CRISPR\/dCas9-based Scn1a gene activation in inhibitory neurons ameliorates epileptic and behavioral phenotypes of Dravet syndrome model mice","volume":"141","author":"Yamagata","year":"2020","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.pedneo.2022.09.004_bib44","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41434-020-00203-z","article-title":"Intra-cisterna magna delivery of an AAV vector with the GLUT1 promoter in a pig recapitulates the physiological expression of SLC2A1","volume":"28","author":"Nakamura","year":"2021","journal-title":"Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/humc.2018.219","article-title":"A gene therapy approach to improve copper metabolism and prevent liver damage in a mouse model of Wilson disease","volume":"30","author":"Greig","year":"2019","journal-title":"Hum Gene Ther Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib46","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jhep.2015.09.014","article-title":"Long-term metabolic correction of Wilson\u2019s disease in a murine model by gene therapy","volume":"64","author":"Murillo","year":"2016","journal-title":"J Hepatol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib47","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.omtm.2022.08.004","article-title":"Full-length ATP7B reconstituted through protein trans-splicing corrects Wilson disease in mice","volume":"26","author":"Padula","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.omtm.2022.06.001","article-title":"High value of 64Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson\u2019s disease","volume":"26","author":"Murillo","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib49","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jhep.2020.11.001","article-title":"Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy","volume":"74","author":"Chand","year":"2021","journal-title":"J Hepatol"},{"key":"10.1016\/j.pedneo.2022.09.004_bib50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.omtm.2017.11.007","article-title":"Emerging issues in AAV-mediated in vivo gene therapy","volume":"8","author":"Colella","year":"2018","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib51","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.omtm.2022.07.018","article-title":"Immunogenicity assessment of AAV-based gene therapies: an IQ consortium industry white paper","volume":"26","author":"Yang","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.pedneo.2022.09.004_bib52","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1089\/hum.2020.167","article-title":"Adeno-associated virus-induced dorsal root ganglion pathology","volume":"31","author":"Hordeaux","year":"2020","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.pedneo.2022.09.004_bib53","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1056\/NEJMoa2005056","article-title":"SOD1 suppression with adeno-associated virus and MicroRNA in familial ALS","volume":"383","author":"Mueller","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.pedneo.2022.09.004_bib54","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1016\/j.ymthe.2022.06.004","article-title":"Evaluating the state of the science for adeno-associated virus integration: an integrated perspective","volume":"30","author":"Sabatino","year":"2022","journal-title":"Mol Ther"}],"container-title":["Pediatrics & Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1875957222002133?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1875957222002133?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T14:56:14Z","timestamp":1761749774000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1875957222002133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":54,"alternative-id":["S1875957222002133"],"URL":"https:\/\/doi.org\/10.1016\/j.pedneo.2022.09.004","relation":{},"ISSN":["1875-9572"],"issn-type":[{"value":"1875-9572","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Adeno-associated virus vector-based gene therapies for pediatric diseases","name":"articletitle","label":"Article Title"},{"value":"Pediatrics & Neonatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pedneo.2022.09.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.","name":"copyright","label":"Copyright"}]}}