{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:36:25Z","timestamp":1792654585325,"version":"4.5.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T00:00:00Z","timestamp":1570060800000},"content-version":"vor","delay-in-days":367,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007608","name":"AgResearch","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004594","name":"Lincoln University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005468","name":"Batten Disease Support and Research Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005468","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006808","name":"University of North Carolina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006808","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1016\/j.ymthe.2018.07.015","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T09:18:20Z","timestamp":1531905500000},"page":"2366-2378","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":65,"title":["Longitudinal In\u00a0Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease"],"prefix":"10.1016","volume":"26","author":[{"given":"Nadia L.","family":"Mitchell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina N.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Wellby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hollie E.","family":"Wicky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Schoderboeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham K.","family":"Barrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy R.","family":"Melzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2018.07.015_bib1","series-title":"The Neuronal Ceroid Lipofuscinoses (Batten Disease)","first-page":"20","article-title":"NCL nomenclature and classification","author":"Williams","year":"2011"},{"key":"10.1016\/j.ymthe.2018.07.015_bib2","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/sj.mt.6300049","article-title":"Enhanced survival of the LINCL mouse following CLN2 gene transfer using the rh.10 rhesus macaque-derived adeno-associated virus vector","volume":"15","author":"Sondhi","year":"2007","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib3","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1089\/hgtb.2012.120","article-title":"Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis","volume":"23","author":"Sondhi","year":"2012","journal-title":"Hum. Gene Ther. Methods"},{"issue":"10 Pt B","key":"10.1016\/j.ymthe.2018.07.015_bib4","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/j.bbadis.2015.06.013","article-title":"Recent studies of ovine neuronal ceroid lipofuscinoses from BARN, the Batten Animal Research Network","volume":"1852","author":"Palmer","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2018.07.015_bib5","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/jnr.23423","article-title":"Enzyme replacement therapy attenuates disease progression in a canine model of late-infantile neuronal ceroid lipofuscinosis (CLN2 disease)","volume":"92","author":"Katz","year":"2014","journal-title":"J.\u00a0Neurosci. Res."},{"issue":"10\u00a0Pt B","key":"10.1016\/j.ymthe.2018.07.015_bib6","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1016\/j.bbadis.2015.04.026","article-title":"Experimental therapies in the neuronal ceroid lipofuscinoses","volume":"1852","author":"Neverman","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2018.07.015_bib7","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/hum.2012.253","article-title":"Partial correction of the CNS lysosomal storage defect in a mouse model of juvenile neuronal ceroid lipofuscinosis by neonatal CNS administration of an adeno-associated virus serotype rh.10 vector expressing the human CLN3 gene","volume":"25","author":"Sondhi","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib8","doi-asserted-by":"crossref","first-page":"9669","DOI":"10.1523\/JNEUROSCI.1635-16.2016","article-title":"Self-complementary AAV9 gene delivery partially corrects pathology associated with juvenile neuronal ceroid lipofuscinosis (CLN3)","volume":"36","author":"Bosch","year":"2016","journal-title":"J.\u00a0Neurosci."},{"issue":"10 Pt B","key":"10.1016\/j.ymthe.2018.07.015_bib9","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1016\/j.bbadis.2015.05.014","article-title":"Towards a new understanding of NCL pathogenesis","volume":"1852","author":"Cooper","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2018.07.015_bib10","series-title":"The Neuronal Ceroid Lipofuscinoses (Batten Disease)","first-page":"284","article-title":"Large animal models","author":"Palmer","year":"2011"},{"key":"10.1016\/j.ymthe.2018.07.015_bib11","doi-asserted-by":"crossref","first-page":"e15752","DOI":"10.1371\/journal.pone.0015752","article-title":"Executive decision-making in the domestic sheep","volume":"6","author":"Morton","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2018.07.015_bib12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jneumeth.2015.08.025","article-title":"A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease","volume":"265","author":"McBride","year":"2016","journal-title":"J.\u00a0Neurosci. Methods"},{"key":"10.1016\/j.ymthe.2018.07.015_bib13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.applanim.2005.06.001","article-title":"Development of a maze test and its application to assess spatial learning and memory in Merino sheep","volume":"96","author":"Lee","year":"2006","journal-title":"Appl. Anim. Behav. Sci."},{"key":"10.1016\/j.ymthe.2018.07.015_bib14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/00480169.2002.36311","article-title":"Neuronal ceroid-lipofuscinosis in Borderdale sheep","volume":"50","author":"Jolly","year":"2002","journal-title":"N.\u00a0Z. Vet. J."},{"key":"10.1016\/j.ymthe.2018.07.015_bib15","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.nbd.2007.09.006","article-title":"A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571+1G>A) leading to excision of exon 3","volume":"29","author":"Frugier","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.ymthe.2018.07.015_bib16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1212\/01.wnl.0000169019.41332.8a","article-title":"A clinical rating scale for Batten disease: reliable and relevant for clinical trials","volume":"65","author":"Marshall","year":"2005","journal-title":"Neurology"},{"key":"10.1016\/j.ymthe.2018.07.015_bib17","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/dmcn.13473","article-title":"Phenotype and natural history of variant late infantile ceroid-lipofuscinosis 5","volume":"59","author":"Simonati","year":"2017","journal-title":"Dev. Med. Child Neurol."},{"key":"10.1016\/j.ymthe.2018.07.015_bib18","series-title":"The Behaviour of Sheep","author":"Lynch","year":"1992"},{"key":"10.1016\/j.ymthe.2018.07.015_bib19","doi-asserted-by":"crossref","first-page":"R561","DOI":"10.1016\/j.cub.2012.05.008","article-title":"Selfish-herd behaviour of sheep under threat","volume":"22","author":"King","year":"2012","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ymthe.2018.07.015_bib20","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.1096","article-title":"Computed tomography provides enhanced techniques for logitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses","author":"Russell","year":"2018","journal-title":"Brain and Behavior"},{"key":"10.1016\/j.ymthe.2018.07.015_bib21","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1089\/hum.2005.16.1484","article-title":"Safety of direct administration of AAV2(CU)hCLN2, a candidate treatment for the central nervous system manifestations of late infantile neuronal ceroid lipofuscinosis, to the brain of rats and nonhuman primates","volume":"16","author":"Hackett","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib22","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1038\/sj.gt.3302549","article-title":"AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL","volume":"12","author":"Sondhi","year":"2005","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib23","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1089\/hum.2011.026","article-title":"Lentiviral-mediated gene transfer to the sheep brain: implications for gene therapy in Batten disease","volume":"22","author":"Linterman","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib24","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1089\/hum.2004.15.1131","article-title":"Clinical protocol. Administration of a replication-deficient adeno-associated virus gene transfer vector expressing the human CLN2 cDNA to the brain of children with late infantile neuronal ceroid lipofuscinosis","volume":"15","author":"Crystal","year":"2004","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib25","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/sj.gt.3301514","article-title":"Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis","volume":"8","author":"McCarty","year":"2001","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib26","doi-asserted-by":"crossref","first-page":"7651","DOI":"10.1128\/JVI.76.15.7651-7660.2002","article-title":"Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size","volume":"76","author":"Yang","year":"2002","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ymthe.2018.07.015_bib27","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."},{"key":"10.1016\/j.ymthe.2018.07.015_bib28","series-title":"Gene vector design and application to treat nervous system disorders","first-page":"1","article-title":"Vector design and considerations for CNS applications","author":"Gray","year":"2011"},{"key":"10.1016\/j.ymthe.2018.07.015_bib29","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1089\/hum.2010.245","article-title":"Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors","volume":"22","author":"Gray","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib30","doi-asserted-by":"crossref","first-page":"313ra180","DOI":"10.1126\/scitranslmed.aac6191","article-title":"AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease","volume":"7","author":"Katz","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2018.07.015_bib31","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1172\/JCI66778","article-title":"Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy","volume":"123","author":"Haurigot","year":"2013","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ymthe.2018.07.015_bib32","doi-asserted-by":"crossref","first-page":"e00401","DOI":"10.1002\/brb3.401","article-title":"Molecular neuropathology of the synapse in sheep with CLN5 Batten disease","volume":"5","author":"Amorim","year":"2015","journal-title":"Brain Behav."},{"key":"10.1016\/j.ymthe.2018.07.015_bib33","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.physbeh.2014.11.037","article-title":"Do I turn left or right? Effects of sex, age, experience and exit route on maze test performance in sheep","volume":"139","author":"Hunter","year":"2015","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.ymthe.2018.07.015_bib34","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s10071-014-0807-3","article-title":"Understanding the concept of a reflective surface: can sheep improve navigational ability through the use of a mirror?","volume":"18","author":"McBride","year":"2015","journal-title":"Anim. Cogn."},{"key":"10.1016\/j.ymthe.2018.07.015_bib35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0376-6357(01)00158-9","article-title":"Human face recognition in sheep: lack of configurational coding and right hemisphere advantage","volume":"55","author":"Peirce","year":"2001","journal-title":"Behav. Processes"},{"key":"10.1016\/j.ymthe.2018.07.015_bib36","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.tvjl.2009.05.029","article-title":"A novel day blindness in sheep: epidemiological, behavioural, electrophysiological and histopathological studies","volume":"185","author":"Shamir","year":"2010","journal-title":"Vet. J."},{"key":"10.1016\/j.ymthe.2018.07.015_bib37","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/mt.2015.114","article-title":"Gene augmentation therapy restores retinal function and visual behavior in a sheep model of CNGA3 achromatopsia","volume":"23","author":"Banin","year":"2015","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib38","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1101\/lm.473907","article-title":"The influence of visual ability on learning and memory performance in 13 strains of mice","volume":"14","author":"Brown","year":"2007","journal-title":"Learn. Mem."},{"key":"10.1016\/j.ymthe.2018.07.015_bib39","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.neurobiolaging.2012.06.016","article-title":"Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice","volume":"34","author":"Yassine","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.ymthe.2018.07.015_bib40","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.tibtech.2008.02.002","article-title":"Biomedical applications of sheep models: from asthma to vaccines","volume":"26","author":"Scheerlinck","year":"2008","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymthe.2018.07.015_bib41","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.1252806","article-title":"The sheep genome illuminates biology of the rumen and lipid metabolism","volume":"344","author":"Jiang","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2018.07.015_bib42","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13023-015-0327-5","article-title":"Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease","volume":"10","author":"Pinnapureddy","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.ymthe.2018.07.015_bib43","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1074\/mcp.M900122-MCP200","article-title":"Mass spectrometry-based protein profiling to determine the cause of lysosomal storage diseases of unknown etiology","volume":"8","author":"Sleat","year":"2009","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.ymthe.2018.07.015_bib44","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cellsig.2017.11.001","article-title":"Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium","volume":"42","author":"Huber","year":"2018","journal-title":"Cell. Signal."},{"key":"10.1016\/j.ymthe.2018.07.015_bib45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.yexcr.2017.04.024","article-title":"CLN5 is cleaved by members of the SPP\/SPPL family to produce a mature soluble protein","volume":"357","author":"Jules","year":"2017","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.ymthe.2018.07.015_bib46","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/mt.2015.187","article-title":"Production of recombinant adeno-associated virus vectors using suspension HEK293 cells and continuous harvest of vector from the culture media for GMP FIX and FLT1 clinical vector","volume":"24","author":"Grieger","year":"2016","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2018.07.015_bib47","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.mri.2012.05.001","article-title":"3D Slicer as an image computing platform for the quantitative imaging network","volume":"30","author":"Fedorov","year":"2012","journal-title":"Magn. Reson. Imaging"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S152500161830340X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S152500161830340X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:46:44Z","timestamp":1777618004000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S152500161830340X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":47,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["S152500161830340X"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2018.07.015","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Longitudinal In\u00a0Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2018.07.015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}