{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:03:43Z","timestamp":1790424223780,"version":"4.1.0"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,12,27]],"date-time":"2020-12-27T00:00:00Z","timestamp":1609027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"INSERM, Aix Marseille University"},{"name":"Association Fran\u00e7aise du Syndrome de Rett"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1016\/j.nbd.2020.105235","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T12:17:48Z","timestamp":1609157868000},"page":"105235","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":54,"special_numbering":"C","title":["Severe offtarget effects following intravenous delivery of AAV9-MECP2 in a female mouse model of Rett syndrome"],"prefix":"10.1016","volume":"149","author":[{"given":"Valerie","family":"Matagne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Borloz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Ehinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Saidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Villard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2020.105235_bb0005","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1093\/hmg\/ddi402","article-title":"A segment of the Mecp2 promoter is sufficient to drive expression in neurons","volume":"14","author":"Adachi","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0010","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1093\/hmg\/ddq096","article-title":"Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development","volume":"19","author":"Alvarez-Saavedra","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0015","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0020","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s12015-016-9670-8","article-title":"Cellular GFP toxicity and immunogenicity: potential confounders in in vivo cell tracking experiments","volume":"12","author":"Ansari","year":"2016","journal-title":"Stem Cell Rev."},{"key":"10.1016\/j.nbd.2020.105235_bb0025","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2174\/156652310793797685","article-title":"Production, purification and characterization of adeno-associated vectors","volume":"10","author":"Ayuso","year":"2010","journal-title":"Curr. Gene Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0030","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0053845","article-title":"Activation of the cellular unfolded protein response by recombinant adeno-associated virus vectors","volume":"8","author":"Balakrishnan","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.nbd.2020.105235_bb0035","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/1440-1681.12453","article-title":"Targeting transgene to the heart and liver with AAV9 by different promoters","volume":"42","author":"Chen","year":"2015","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"10.1016\/j.nbd.2020.105235_bb0040","doi-asserted-by":"crossref","first-page":"42790","DOI":"10.1038\/srep42790","article-title":"Regulation of mRNA splicing by MeCP2 via epigenetic modifications in the brain","volume":"7","author":"Cheng","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2020.105235_bb0045","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nbt.3440","article-title":"Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain","volume":"34","author":"Deverman","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.nbd.2020.105235_bb0050","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/mt.2009.71","article-title":"Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons","volume":"17","author":"Duque","year":"2009","journal-title":"Mol. Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0055","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.nbd.2020.105235_bb0060","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/mt.2012.200","article-title":"Improved survival and reduced phenotypic severity following AAV9\/MECP2 gene transfer to neonatal and juvenile male Mecp2 knockout mice","volume":"21","author":"Gadalla","year":"2013","journal-title":"Mol. Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0065","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.omtm.2017.04.007","article-title":"Development of a novel AAV gene therapy cassette with improved safety features and efficacy in a mouse model of Rett syndrome","volume":"5","author":"Gadalla","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.nbd.2020.105235_bb0070","doi-asserted-by":"crossref","first-page":"13612","DOI":"10.1523\/JNEUROSCI.1854-13.2013","article-title":"Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome","volume":"33","author":"Garg","year":"2013","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2020.105235_bb0075","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/mt.2011.72","article-title":"Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates","volume":"19","author":"Gray","year":"2011","journal-title":"Mol. Ther."},{"issue":"315","key":"10.1016\/j.nbd.2020.105235_bb0080","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1126\/science.1138389","article-title":"Reversal of neurological defects in a mouse model of Rett syndrome","volume":"80","author":"Guy","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.nbd.2020.105235_bb0085","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1651-2227.1995.tb13809.x","article-title":"Rett syndrome: clinical peculiarities and biological mysteries","volume":"84","author":"Hagberg","year":"1995","journal-title":"Acta Paediatr."},{"key":"10.1016\/j.nbd.2020.105235_bb0090","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1089\/hum.2016.087","article-title":"Adeno-associated virus-based gene therapy for CNS diseases","volume":"27","author":"Hocquemiller","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0095","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.ymthe.2018.01.018","article-title":"The neurotropic properties of AAV-PHP.B are limited to C57BL\/6J mice","volume":"26","author":"Hordeaux","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0100","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/adc.77.5.463c","article-title":"Immaturity of medullary cardiorespiratory neurones leading to inappropriate autonomic reactions as a likely cause of sudden death in Rett\u2019s syndrome","volume":"77","author":"Julu","year":"1997","journal-title":"Arch. Dis. Child."},{"key":"10.1016\/j.nbd.2020.105235_bb0105","article-title":"A role for metabolism in Rett syndrome pathogenesis: new clinical findings and potential treatment targets","volume":"1","author":"Justice","year":"2013","journal-title":"Rare Dis."},{"key":"10.1016\/j.nbd.2020.105235_bb0110","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1242\/dmm.011007","article-title":"Preclinical research in Rett syndrome: setting the foundation for translational success","volume":"5","author":"Katz","year":"2012","journal-title":"Dis. Model. Mech."},{"issue":"Suppl. 1","key":"10.1016\/j.nbd.2020.105235_bb0115","first-page":"71","article-title":"Rett syndrome: analysis of deaths in the British survey","volume":"6","author":"Kerr","year":"1997","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"10.1016\/j.nbd.2020.105235_bb0120","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/cld.653","article-title":"Patterns of necrosis in liver disease","volume":"10","author":"Krishna","year":"2017","journal-title":"Clin Liver Dis (Hoboken)"},{"key":"10.1016\/j.nbd.2020.105235_bb0125","first-page":"3029","article-title":"MeCP2 co-ordinates liver lipid metabolism with the NCoR1\/HDAC3 corepressor complex","volume":"25","author":"Kyle","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0130","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nbd.2015.03.009","article-title":"Circadian rhythm disruption in a mouse model of Rett syndrome circadian disruption in RTT","volume":"77","author":"Li","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.nbd.2020.105235_bb0135","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1006\/bbrc.1999.0954","article-title":"Is green fluorescent protein toxic to the living cells?","volume":"260","author":"Liu","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.nbd.2020.105235_bb0140","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.nbd.2020.105235_bb0145","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1172\/JCI78167","article-title":"MECP2 disorders: from the clinic to mice and back","volume":"125","author":"Lombardi","year":"2015","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.nbd.2020.105235_bb0150","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.52629","article-title":"Whole brain delivery of an instability-prone Mecp2 transgene improves behavioral and molecular pathological defects in mouse models of Rett syndrome","volume":"9","author":"Luoni","year":"2020","journal-title":"Elife"},{"key":"10.1016\/j.nbd.2020.105235_bb0155","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrg3897","article-title":"Rett syndrome: a complex disorder with simple roots","volume":"16","author":"Lyst","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0160","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2016.12.009","article-title":"A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome","volume":"99","author":"Matagne","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.nbd.2020.105235_bb0165","doi-asserted-by":"crossref","first-page":"494","DOI":"10.4238\/vol10-1gmr1023","article-title":"Expression of GFP can influence aging and climbing ability in Drosophila","volume":"10","author":"Mawhinney","year":"2011","journal-title":"Genet. Mol. Res."},{"key":"10.1016\/j.nbd.2020.105235_bb0170","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/gt.2011.64","article-title":"Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine","volume":"19","author":"McIntosh","year":"2012","journal-title":"Gene Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0175","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1326-2-16","article-title":"Design of an improved set of oligonucleotide primers for genotyping MeCP2tm1.1Bird KO mice by PCR","volume":"2","author":"Miralv\u00e8s","year":"2007","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.nbd.2020.105235_bb0180","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/nbt1097-961","article-title":"Applications of the green fluorescent protein in cell biology and biotechnology","volume":"15","author":"Misteli","year":"1997","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.nbd.2020.105235_bb0185","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.neubiorev.2018.12.009","article-title":"Disturbed redox homeostasis and oxidative stress: potential players in the developmental regression in Rett syndrome","volume":"98","author":"M\u00fcller","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.nbd.2020.105235_bb0190","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1523\/JNEUROSCI.6000-11.2012","article-title":"A mouse model for MeCP2 duplication syndrome: MeCP2 overexpression impairs learning and memory and synaptic transmission","volume":"32","author":"Na","year":"2012","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2020.105235_bb0195","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/ana.410420104","article-title":"Rett syndrome: a disorder affecting early brain growth","volume":"42","author":"Naidu","year":"1997","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2020.105235_bb0200","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett syndrome: revised diagnostic criteria and nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.nbd.2020.105235_bb2020","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbr.2010.08.011","article-title":"Progressive motor and respiratory metabolism deficits in post-weaning Mecp2-null male mice","volume":"216","author":"Pratte","year":"2011","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.nbd.2020.105235_bb0205","doi-asserted-by":"crossref","first-page":"7951","DOI":"10.1523\/JNEUROSCI.0169-11.2011","article-title":"Complexities of Rett syndrome and MeCP2","volume":"31","author":"Samaco","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.nbd.2020.105235_bb0210","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/hmg\/dds406","article-title":"Female Mecp2(+\/\u2212) mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies","volume":"22","author":"Samaco","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0215","doi-asserted-by":"crossref","first-page":"12297","DOI":"10.1038\/s41598-017-12069-0","article-title":"Retention of mitochondria in mature human red blood cells as the result of autophagy impairment in rett syndrome","volume":"7","author":"Sbardella","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.nbd.2020.105235_bb0220","doi-asserted-by":"crossref","first-page":"165793","DOI":"10.1016\/j.bbadis.2020.165793","article-title":"Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations","author":"Sbardella","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. basis Dis."},{"key":"10.1016\/j.nbd.2020.105235_bb0225","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3389\/fmicb.2014.00250","article-title":"Cellular unfolded protein response against viruses used in gene therapy","volume":"5","author":"Sen","year":"2014","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.nbd.2020.105235_bb0230","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1089\/hum.2020.217","article-title":"Re: \u201cmoving forward after two deaths in a gene therapy trial of myotubular myopathy\u201d by Wilson and flotte","volume":"31","author":"Shieh","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.nbd.2020.105235_bb0235","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.omtm.2017.04.006","article-title":"Improved MECP2 gene therapy extends the survival of MeCP2-null mice without apparent toxicity after intracisternal delivery","volume":"5","author":"Sinnett","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.nbd.2020.105235_bb0240","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/hmg\/ddy338","article-title":"Loss of MeCP2 in immature neurons leads to impaired network integration","volume":"28","author":"Sun","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.nbd.2020.105235_bb0245","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.braindev.2018.03.010","article-title":"The course of awake breathing disturbances across the lifespan in Rett syndrome","volume":"40","author":"Tarquinio","year":"2018","journal-title":"Brain Dev."},{"key":"10.1016\/j.nbd.2020.105235_bb0250","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/nature24058","article-title":"Radically truncated MeCP2 rescues Rett syndrome-like neurological defects","volume":"550","author":"Tillotson","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.nbd.2020.105235_bb0255","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/gtc.12305","article-title":"Disruption of MeCP2 attenuates circadian rhythm in CRISPR\/Cas9-based Rett syndrome model mouse","volume":"20","author":"Tsuchiya","year":"2015","journal-title":"Genes Cells"},{"key":"10.1016\/j.nbd.2020.105235_bb1010","doi-asserted-by":"crossref","first-page":"11521","DOI":"10.1523\/JNEUROSCI.4373-05.2005","article-title":"Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice","volume":"25","author":"Viemari","year":"2005","journal-title":"J Neurosci."},{"key":"10.1016\/j.nbd.2020.105235_bb0260","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/gt.2014.4","article-title":"Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model","volume":"21","author":"Wang","year":"2014","journal-title":"Gene Ther."}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996120305118?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996120305118?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:23:21Z","timestamp":1760851401000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996120305118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":54,"alternative-id":["S0969996120305118"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2020.105235","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Severe offtarget effects following intravenous delivery of AAV9-MECP2 in a female mouse model of Rett syndrome","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2020.105235","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"105235"}}