{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:41:46Z","timestamp":1773272506086,"version":"3.50.1"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T00:00:00Z","timestamp":1485302400000},"content-version":"vor","delay-in-days":390,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Nucleic Acids"],"published-print":{"date-parts":[[2016]]},"DOI":"10.1038\/mtna.2016.86","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T11:20:52Z","timestamp":1478604052000},"page":"e383","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia"],"prefix":"10.1016","volume":"5","author":[{"given":"Alastair G","family":"Kerr","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence CS","family":"Tam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley B","family":"Hale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Cioroch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Douglas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith M","family":"Channon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Wade-Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1038\/mtna.2016.86_bib1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.ge.24.120190.001025","article-title":"The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein","volume":"24","author":"Hobbs","year":"1990","journal-title":"Annu Rev Genet"},{"key":"10.1038\/mtna.2016.86_bib2","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.2147\/VHRM.S8283","article-title":"Optimal management of familial hypercholesterolemia: treatment and management strategies","volume":"6","author":"Nemati","year":"2010","journal-title":"Vasc Health Risk Manag"},{"key":"10.1038\/mtna.2016.86_bib3","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.atherosclerosis.2005.11.016","article-title":"Autosomal recessive hypercholesterolemia (ARH) and homozygous familial hypercholesterolemia (FH): a phenotypic comparison","volume":"188","author":"Pisciotta","year":"2006","journal-title":"Atherosclerosis"},{"key":"10.1038\/mtna.2016.86_bib4","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s001099900045","article-title":"Nonphysiological overexpression of low-density lipoprotein receptors causes pathological intracellular lipid accumulation and the formation of cholesterol and cholesteryl ester crystals in vitro","volume":"77","author":"Heeren","year":"1999","journal-title":"J Mol Med (Berl)"},{"key":"10.1038\/mtna.2016.86_bib5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/jgm.473","article-title":"Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage","volume":"6","author":"Cichon","year":"2004","journal-title":"J Gene Med"},{"key":"10.1038\/mtna.2016.86_bib6","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/82444","article-title":"Stable correction of a genetic deficiency in human cells by an episome carrying a 115\u2009kb genomic transgene","volume":"18","author":"Wade-Martins","year":"2000","journal-title":"Nat Biotechnol"},{"key":"10.1038\/mtna.2016.86_bib7","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jgm.1041","article-title":"Delivery and long-term expression of a 135\u2009kb LDLR genomic DNA locus in vivo by hydrodynamic tail vein injection","volume":"9","author":"Hibbitt","year":"2007","journal-title":"J Gene Med"},{"key":"10.1038\/mtna.2016.86_bib8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/mt.2009.249","article-title":"Long-term physiologically regulated expression of the low-density lipoprotein receptor in vivo using genomic DNA mini-gene constructs","volume":"18","author":"Hibbitt","year":"2010","journal-title":"Mol Ther"},{"key":"10.1038\/mtna.2016.86_bib9","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/gt.2011.103","article-title":"RNAi-mediated knockdown of HMG CoA reductase enhances gene expression from physiologically regulated low-density lipoprotein receptor therapeutic vectors in vivo","volume":"19","author":"Hibbitt","year":"2012","journal-title":"Gene Ther"},{"key":"10.1038\/mtna.2016.86_bib10","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1161\/01.ATV.0000258790.35810.02","article-title":"A diet-induced hypercholesterolemic murine model to study atherogenesis without obesity and metabolic syndrome","volume":"27","author":"Hartvigsen","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3 Suppl","key":"10.1038\/mtna.2016.86_bib11","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jacl.2011.04.003","article-title":"Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia","volume":"5","author":"Goldberg","year":"2011","journal-title":"J Clin Lipidol"},{"key":"10.1038\/mtna.2016.86_bib12","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1056\/NEJM198412273112603","article-title":"Liver transplantation to provide low-density-lipoprotein receptors and lower plasma cholesterol in a child with homozygous familial hypercholesterolemia","volume":"311","author":"Bilheimer","year":"1984","journal-title":"N Engl J Med"},{"key":"10.1038\/mtna.2016.86_bib13","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1172\/JCI117725","article-title":"In vivo gene therapy for hyperlipidemia: phenotypic correction in Watanabe rabbits by hepatic delivery of the rabbit LDL receptor gene","volume":"95","author":"Li","year":"1995","journal-title":"J Clin Invest"},{"key":"10.1038\/mtna.2016.86_bib14","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/1074-7613(94)90074-4","article-title":"MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses","volume":"1","author":"Yang","year":"1994","journal-title":"Immunity"},{"key":"10.1038\/mtna.2016.86_bib15","doi-asserted-by":"crossref","first-page":"e13424","DOI":"10.1371\/journal.pone.0013424","article-title":"Gene therapy in a humanized mouse model of familial hypercholesterolemia leads to marked regression of atherosclerosis","volume":"5","author":"Kassim","year":"2010","journal-title":"PLoS One"},{"key":"10.1038\/mtna.2016.86_bib16","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/mt.2015.221","article-title":"Sleeping beauty transposon vectors in liver-directed gene delivery of LDLR and VLDLR for gene therapy of familial hypercholesterolemia","volume":"24","author":"Turunen","year":"2016","journal-title":"Mol Ther"},{"key":"10.1038\/mtna.2016.86_bib17","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature04791","article-title":"Fatality in mice due to oversaturation of cellular microRNA\/short hairpin RNA pathways","volume":"441","author":"Grimm","year":"2006","journal-title":"Nature"},{"key":"10.1038\/mtna.2016.86_bib18","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1073\/pnas.0801775105","article-title":"Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi","volume":"105","author":"McBride","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/mtna.2016.86_bib19","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1194\/jlr.M053207","article-title":"PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE","volume":"55","author":"Ason","year":"2014","journal-title":"J Lipid Res"},{"issue":"8934","key":"10.1038\/mtna.2016.86_bib20","first-page":"1383","article-title":"Randomised trial of cholesterol lowering 4444 patients with coronoary heart disease: the Scandinavian Simvastatin Survival Study (4S)","volume":"344","author":"Scandinavian Simvastatin Survival Study Group","year":"1994","journal-title":"Lancet"},{"key":"10.1038\/mtna.2016.86_bib21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1161\/01.ATV.14.1.133","article-title":"ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree","volume":"14","author":"Nakashima","year":"1994","journal-title":"Arterioscler Thromb"},{"key":"10.1038\/mtna.2016.86_bib22","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1161\/01.CIR.92.5.1355","article-title":"A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association","volume":"92","author":"Stary","year":"1995","journal-title":"Circulation"},{"key":"10.1038\/mtna.2016.86_bib23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.virol.2004.04.032","article-title":"Strain-specific rate of shutdown of CMV enhancer activity in murine liver confirmed by use of persistent [E1(-), E2b(-)] adenoviral vectors","volume":"325","author":"Everett","year":"2004","journal-title":"Virology"},{"key":"10.1038\/mtna.2016.86_bib24","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/sj.gt.3302469","article-title":"Hydrodynamic liver gene transfer mechanism involves transient sinusoidal blood stasis and massive hepatocyte endocytic vesicles","volume":"12","author":"Crespo","year":"2005","journal-title":"Gene Ther"},{"key":"10.1038\/mtna.2016.86_bib25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/sj.gt.3302865","article-title":"Structural impact of hydrodynamic injection on mouse liver","volume":"14","author":"Suda","year":"2007","journal-title":"Gene Ther"},{"key":"10.1038\/mtna.2016.86_bib26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1056\/NEJM200301163480314","article-title":"A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency","volume":"348","author":"Hacein-Bey-Abina","year":"2003","journal-title":"N Engl J Med"},{"key":"10.1038\/mtna.2016.86_bib27","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/sj.gt.3302310","article-title":"Low-density lipoprotein receptor gene therapy using helper-dependent adenovirus produces long-term protection against atherosclerosis in a mouse model of familial hypercholesterolemia","volume":"11","author":"Nomura","year":"2004","journal-title":"Gene Ther"},{"key":"10.1038\/mtna.2016.86_bib28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/hum.2012.108","article-title":"Adeno-associated virus serotype 8 gene therapy leads to significant lowering of plasma cholesterol levels in humanized mouse models of homozygous and heterozygous familial hypercholesterolemia","volume":"24","author":"Kassim","year":"2013","journal-title":"Hum Gene Ther"},{"key":"10.1038\/mtna.2016.86_bib29","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0022-2275(20)36966-2","article-title":"Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins","volume":"34","author":"Greeve","year":"1993","journal-title":"J Lipid Res"},{"key":"10.1038\/mtna.2016.86_bib30","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1172\/JCI4164","article-title":"Lipoprotein clearance mechanisms in LDL receptor-deficient \u201cApo-B48-only\u201d and \u201cApo-B100-only\u201d mice","volume":"102","author":"V\u00e9niant","year":"1998","journal-title":"J Clin Invest"},{"key":"10.1038\/mtna.2016.86_bib31","doi-asserted-by":"crossref","first-page":"e107203","DOI":"10.1371\/journal.pone.0107203","article-title":"Safety assessment of liver-targeted hydrodynamic gene delivery in dogs","volume":"9","author":"Kamimura","year":"2014","journal-title":"PLoS One"},{"key":"10.1038\/mtna.2016.86_bib32","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1038\/mtna.2013.52","article-title":"Parameters affecting image-guided, hydrodynamic gene delivery to swine liver","volume":"2","author":"Kamimura","year":"2013","journal-title":"Mol Ther Nucleic Acids"},{"key":"10.1038\/mtna.2016.86_bib33","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s40265-015-0460-4","article-title":"Evolocumab: first global approval","volume":"75","author":"Markham","year":"2015","journal-title":"Drugs"},{"key":"10.1038\/mtna.2016.86_bib34","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1093\/nar\/gkm570","article-title":"An S\/MAR-based infectious episomal genomic DNA expression vector provides long-term regulated functional complementation of LDLR deficiency","volume":"35","author":"Lufino","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"10.1038\/mtna.2016.86_bib35","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S1525-0016(02)00060-6","article-title":"In vitro and in vivo comparative study of chimeric liver-specific promoters","volume":"7","author":"Kramer","year":"2003","journal-title":"Mol Ther"},{"key":"10.1038\/mtna.2016.86_bib36","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.ymthe.2004.01.015","article-title":"Long-term lowering of plasma cholesterol levels in LDL-receptor-deficient WHHL rabbits by gene therapy","volume":"9","author":"Kankkonen","year":"2004","journal-title":"Mol Ther"}],"container-title":["Molecular Therapy - Nucleic Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253117301051?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2162253117301051?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:28:32Z","timestamp":1761874112000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2162253117301051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":36,"alternative-id":["S2162253117301051"],"URL":"https:\/\/doi.org\/10.1038\/mtna.2016.86","relation":{},"ISSN":["2162-2531"],"issn-type":[{"value":"2162-2531","type":"print"}],"subject":[],"published":{"date-parts":[[2016]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Nucleic Acids","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/mtna.2016.86","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2016 Official journal of the American Society of Gene & Cell Therapy. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"e383"}}