{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:54:28Z","timestamp":1778637268601,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>In the era of genomic medicine, diagnoses of rare paediatric neurological diseases are increasing. Many are untreatable and life\u2010limiting, leading to an exceptional increase in gene therapy development. It is estimated that 20 gene therapy products will have received approval from the US Food and Drug Administration by 2025. With viral gene therapy considered a potential single\u2010dose cure for patients with spinal muscular atrophy type 1 as one example, and contemporaneously tragically resulting in the deaths of three male children with X\u2010linked myotubular myopathy receiving high\u2010dose gene therapy in 2020, what is the current state of gene therapy? What is behind the decades of hype around viral gene therapy and is it high impact, but high risk? In this review, we outline principles of viral gene therapy development and summarize the most recent clinical evidence for the therapeutic effect of gene therapy in paediatric neurological diseases. We discuss adeno\u2010associated virus and lentiviral vectors, antisense oligonucleotides, emerging genetic editing approaches, and current limitations that the field still faces.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"box\" position=\"anchor\"><jats:caption><jats:title>What this paper adds<\/jats:title><\/jats:caption><jats:p>\n<jats:list list-type=\"bullet\">\n\n<jats:list-item><jats:p>Viral gene therapy development and clinically used transgenes, regulatory elements, capsids, dosage, and delivery routes are summarized.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Viral gene therapy for 18 childhood neurological disorders involving over 600 children in 40 clinical trials are reviewed.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.14885","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T07:08:18Z","timestamp":1617952098000},"page":"1019-1029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Viral gene therapy for paediatric neurological diseases: progress to clinical reality"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5699-9587","authenticated-orcid":false,"given":"Riccardo","family":"Privolizzi","sequence":"first","affiliation":[{"name":"Gene Transfer Technology Group EGA Institute for Women\u2019s Health University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3517-2200","authenticated-orcid":false,"given":"Wing Sum","family":"Chu","sequence":"additional","affiliation":[{"name":"Pharmacy Department The Royal Marsden NHS Foundation Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-3099","authenticated-orcid":false,"given":"Maha","family":"Tijani","sequence":"additional","affiliation":[{"name":"Immune Regulation and Tumour Immunotherapy Group Cancer Institute University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-9965","authenticated-orcid":false,"given":"Joanne","family":"Ng","sequence":"additional","affiliation":[{"name":"Gene Transfer Technology Group EGA Institute for Women\u2019s Health University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0508-0"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1353\/pbm.1966.0027"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.08.016"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200301163480314"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108046"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802268"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706198"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0205-4"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.017"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00014"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31661"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805817"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3763"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2019.102115"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.148"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0049-9"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.022"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2013.238"},{"key":"e_1_2_15_22_1","unstructured":"Lysogene confirms child\u2019s death in phase II\/III gene therapy trial.Genet Eng Biotechnol News2020.https:\/\/www.genengnews.com\/news\/lysogene\u2010confirms\u2010childs\u2010death\u2010in\u2010phase\u2010ii\u2010iii\u2010gene\u2010therapy\u2010trial\/(accessed 12 February 2021)."},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.11.012"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0106-7"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy212"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003454"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1700554"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30374-9"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702752"},{"key":"e_1_2_15_30_1","unstructured":"Spinraza access by country.TreatSMA2019.https:\/\/www.treatsma.uk\/treatments\/spinraza\/spinraza\u2010access\u2010by\u2010country\/(accessed 12 February 2021)."},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813279"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.05.005"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1484"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1549"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2019.006"},{"key":"e_1_2_15_36_1","first-page":"306","article-title":"ASPIRO phase 1\/2 gene therapy trial in X\u2010linked myotubular myopathy (XLMTM): update on preliminary safety and efficacy findings","volume":"27","author":"Shieh PB","year":"2019","journal-title":"Mol Ther"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143780"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2020.217"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.43"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.08.018"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c29356"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003640"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(17)30125-6"},{"key":"e_1_2_15_44_1","unstructured":"Solid Biosciences provides SGT\u2010001 program update.Solid Biosciences Inc. Press Releases2020.https:\/\/www.solidbio.com\/about\/media\/press\u2010releases\/solid\u2010biosciences\u2010announces\u2010fda\u2010lifts\u2010clinical\u2010hold\u2010on\u2010ignite\u2010dmd\u2010clinical\u2010trial(accessed 12 February 2021)."},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.150"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.04.007"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79213"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3389"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-126007"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1711-4"}],"container-title":["Developmental Medicine &amp; Child Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.14885","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dmcn.14885","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.14885","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T05:51:39Z","timestamp":1705557099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dmcn.14885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,9]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1111\/dmcn.14885"],"URL":"https:\/\/doi.org\/10.1111\/dmcn.14885","archive":["Portico"],"relation":{},"ISSN":["0012-1622","1469-8749"],"issn-type":[{"value":"0012-1622","type":"print"},{"value":"1469-8749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,9]]},"assertion":[{"value":"2021-03-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}