{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:18:40Z","timestamp":1791137920354,"version":"4.1.0"},"reference-count":57,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T00:00:00Z","timestamp":1475798400000},"content-version":"vor","delay-in-days":767,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2014,9]]},"DOI":"10.1038\/mt.2014.131","type":"journal-article","created":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T11:21:22Z","timestamp":1405682482000},"page":"1614-1624","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"title":["Hyperactive PiggyBac Transposons for Sustained and Robust Liver-targeted Gene Therapy"],"prefix":"10.1016","volume":"22","author":[{"given":"Mario","family":"Di Matteo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emira","family":"Samara-Kuko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie J","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon N","family":"Waddingon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"McVey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinee KL","family":"Chuah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"VandenDriessche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/mt.2014.131_bib1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nrg2988","article-title":"Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges","volume":"12","author":"Mingozzi","year":"2011","journal-title":"Nat Rev Genet"},{"key":"10.1038\/mt.2014.131_bib2","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1006\/mthe.2000.0075","article-title":"Inclusion of the hepatic locus control region, an intron, and untranslated region increases and stabilizes hepatic factor IX gene expression in vivo but not in vitro","volume":"1","author":"Miao","year":"2000","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib3","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1517\/14712598.2012.684875","article-title":"Recent developments in transposon-mediated gene therapy","volume":"12","author":"Di Matteo","year":"2012","journal-title":"Expert Opin Biol Ther"},{"key":"10.1038\/mt.2014.131_bib4","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ng.343","article-title":"Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates","volume":"41","author":"M\u00e1t\u00e9s","year":"2009","journal-title":"Nat Genet"},{"key":"10.1038\/mt.2014.131_bib5","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0042-6822(89)90117-7","article-title":"Transposon mutagenesis of baculoviruses: analysis of Trichoplusia ni transposon IFP2 insertions within the FP-locus of nuclear polyhedrosis viruses","volume":"172","author":"Cary","year":"1989","journal-title":"Virology"},{"key":"10.1038\/mt.2014.131_bib6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cell.2005.07.013","article-title":"Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice","volume":"122","author":"Ding","year":"2005","journal-title":"Cell"},{"key":"10.1038\/mt.2014.131_bib7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/sj.mt.6300028","article-title":"PiggyBac transposon-mediated gene transfer in human cells","volume":"15","author":"Wilson","year":"2007","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib8","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1093\/nar\/gkr764","article-title":"Mobilization of giant piggyBac transposons in the mouse genome","volume":"39","author":"Li","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"10.1038\/mt.2014.131_bib9","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1182\/blood-2009-04-210427","article-title":"Emerging potential of transposons for gene therapy and generation of induced pluripotent stem cells","volume":"114","author":"VandenDriessche","year":"2009","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib10","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nature07863","article-title":"piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells","volume":"458","author":"Woltjen","year":"2009","journal-title":"Nature"},{"key":"10.1038\/mt.2014.131_bib11","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1038\/mt.2009.234","article-title":"PiggyBac transposon-based inducible gene expression in vivo after somatic cell gene transfer","volume":"17","author":"Saridey","year":"2009","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib12","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/mt.2009.302","article-title":"piggyBac transposon-mediated long-term gene expression in mice","volume":"18","author":"Nakanishi","year":"2010","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib13","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/hum.2011.138","article-title":"Hyperactive piggyBac gene transfer in human cells and in vivo","volume":"23","author":"Doherty","year":"2012","journal-title":"Hum Gene Ther"},{"key":"10.1038\/mt.2014.131_bib14","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1038\/mtna.2012.12","article-title":"A hyperactive transposase promotes persistent gene transfer of a piggyBac DNA transposon","volume":"1","author":"Burnight","year":"2012","journal-title":"Mol Ther Nucleic Acids"},{"key":"10.1038\/mt.2014.131_bib15","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1096\/fj.13-232090","article-title":"An adaptable system for improving transposon-based gene expression in vivo via transient transgene repression","volume":"27","author":"Doherty","year":"2013","journal-title":"FASEB J"},{"issue":"suppl. 1","key":"10.1038\/mt.2014.131_bib16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/jth.12215","article-title":"Gene therapy for hemophilia","volume":"11","author":"Chuah","year":"2013","journal-title":"J Thromb Haemost"},{"key":"10.1038\/mt.2014.131_bib17","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1073\/pnas.1008322108","article-title":"A hyperactive piggyBac transposase for mammalian applications","volume":"108","author":"Yusa","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/mt.2014.131_bib18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.stem.2009.07.011","article-title":"An efficient and reversible transposable system for gene delivery and lineage-specific differentiation in human embryonic stem cells","volume":"5","author":"Lacoste","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1038\/mt.2014.131_bib19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1472-6750-11-28","article-title":"Genome-wide target profiling of piggyBac and Tol2 in HEK 293: pros and cons for gene discovery and gene therapy","volume":"11","author":"Meir","year":"2011","journal-title":"BMC Biotechnol"},{"key":"10.1038\/mt.2014.131_bib20","doi-asserted-by":"crossref","DOI":"10.1038\/mt.2014.114","article-title":"Liver-specific transcriptional modules identified by genome-wide in silico analysis enable efficient gene therapy in mice and non-human primates","author":"Chuah","year":"2014","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib21","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1182\/blood-2013-10-534032","article-title":"Computationally designed liver-specific transcriptional modules and hyperactive factor IX improve hepatic gene therapy","volume":"123","author":"Nair","year":"2014","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib22","doi-asserted-by":"crossref","DOI":"10.1002\/hep.27104","article-title":"Treatment of phenylketonuria using minicircle-based naked-DNA gene transfer to murine liver","author":"Viecelli","year":"2014","journal-title":"Hepatology"},{"key":"10.1038\/mt.2014.131_bib23","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1056\/NEJMoa0904377","article-title":"X-linked thrombophilia with a mutant factor IX (factor IX Padua)","volume":"361","author":"Simioni","year":"2009","journal-title":"N Engl J Med"},{"key":"10.1038\/mt.2014.131_bib24","doi-asserted-by":"crossref","first-page":"4517","DOI":"10.1182\/blood-2012-05-432591","article-title":"Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice","volume":"120","author":"Cantore","year":"2012","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib25","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1093\/nar\/gkm446","article-title":"Generation of an inducible and optimized piggyBac transposon system","volume":"35","author":"Cadi\u00f1anos","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"10.1038\/mt.2014.131_bib26","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/sj.mt.6300355","article-title":"Optimization of self-complementary AAV vectors for liver-directed expression results in sustained correction of hemophilia B at low vector dose","volume":"16","author":"Wu","year":"2008","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib27","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1182\/blood-2005-10-4035","article-title":"Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver","volume":"107","author":"Nathwani","year":"2006","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib28","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/sj.gt.3302231","article-title":"Silencing of episomal transgene expression by plasmid bacterial DNA elements in vivo","volume":"11","author":"Chen","year":"2004","journal-title":"Gene Ther"},{"key":"10.1038\/mt.2014.131_bib29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/hum.2009.212","article-title":"Transgene loss and changes in the promoter methylation status as determinants for expression duration in nonviral gene transfer for factor IX","volume":"22","author":"Sch\u00fcttrumpf","year":"2011","journal-title":"Hum Gene Ther"},{"key":"10.1038\/mt.2014.131_bib30","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/nrg3051","article-title":"Understanding the contribution of synonymous mutations to human disease","volume":"12","author":"Sauna","year":"2011","journal-title":"Nat Rev Genet"},{"key":"10.1038\/mt.2014.131_bib31","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1182\/blood-2010-05-282707","article-title":"Codon optimization of human factor VIII cDNAs leads to high-level expression","volume":"117","author":"Ward","year":"2011","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib32","first-page":"4253","article-title":"Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse","volume":"43","author":"Vesselinovitch","year":"1983","journal-title":"Cancer Res"},{"key":"10.1038\/mt.2014.131_bib33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4254\/wjh.v2.i1.16","article-title":"Targeting c-Myc as a novel approach for hepatocellular carcinoma","volume":"2","author":"Lin","year":"2010","journal-title":"World J Hepatol"},{"key":"10.1038\/mt.2014.131_bib34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/nat.2010.0248","article-title":"Immune activation and target organ damage are consequences of hydrodynamic treatment but not delivery of naked siRNAs in mice","volume":"21","author":"R\u00e1cz","year":"2011","journal-title":"Nucleic Acid Ther"},{"key":"10.1038\/mt.2014.131_bib35","doi-asserted-by":"crossref","first-page":"e11367","DOI":"10.1371\/journal.pone.0011367","article-title":"Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma","volume":"5","author":"Woodard","year":"2010","journal-title":"PLoS One"},{"key":"10.1038\/mt.2014.131_bib36","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1182\/blood-2012-06-440123","article-title":"The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy","volume":"120","author":"Finn","year":"2012","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib37","first-page":"2086","article-title":"Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice","volume":"119","author":"Kren","year":"2009","journal-title":"J Clin Invest"},{"key":"10.1038\/mt.2014.131_bib38","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/gt.2009.13","article-title":"Indoleamine 2,3-dioxygenase attenuates inhibitor development in gene-therapy-treated hemophilia A mice","volume":"16","author":"Liu","year":"2009","journal-title":"Gene Ther"},{"key":"10.1038\/mt.2014.131_bib39","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.ymthe.2005.11.021","article-title":"Sustained FVIII expression and phenotypic correction of hemophilia A in neonatal mice using an endothelial-targeted sleeping beauty transposon","volume":"13","author":"Liu","year":"2006","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib40","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1182\/blood-2004-09-3496","article-title":"Phenotypic correction and long-term expression of factor VIII in hemophilic mice by immunotolerization and nonviral gene transfer using the Sleeping Beauty transposon system","volume":"105","author":"Ohlfest","year":"2005","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib41","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/75568","article-title":"Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system","volume":"25","author":"Yant","year":"2000","journal-title":"Nat Genet"},{"key":"10.1038\/mt.2014.131_bib42","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1089\/hum.2005.16.558","article-title":"Increased maintenance and persistence of transgenes by excision of expression cassettes from plasmid sequences in vivo","volume":"16","author":"Riu","year":"2005","journal-title":"Hum Gene Ther"},{"key":"10.1038\/mt.2014.131_bib43","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1172\/JCI200316887","article-title":"Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer","volume":"111","author":"Mingozzi","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1038\/mt.2014.131_bib44","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1002\/hep.24230","article-title":"Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk","volume":"53","author":"M\u00e1trai","year":"2011","journal-title":"Hepatology"},{"key":"10.1038\/mt.2014.131_bib45","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1182\/blood-2009-04-214569","article-title":"In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance","volume":"114","author":"Annoni","year":"2009","journal-title":"Blood"},{"key":"10.1038\/mt.2014.131_bib46","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1136\/gutjnl-2011-301116","article-title":"Adaptive immunity suppresses formation and progression of diethylnitrosamine-induced liver cancer","volume":"61","author":"Schneider","year":"2012","journal-title":"Gut"},{"key":"10.1038\/mt.2014.131_bib47","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1038\/sj.mt.6300314","article-title":"Hydrodynamic gene delivery: its principles and applications","volume":"15","author":"Suda","year":"2007","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib48","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1089\/10430349950017734","article-title":"High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA","volume":"10","author":"Zhang","year":"1999","journal-title":"Hum Gene Ther"},{"key":"10.1038\/mt.2014.131_bib49","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/mt.2011.129","article-title":"Manipulating piggyBac transposon chromosomal integration site selection in human cells","volume":"19","author":"Kettlun","year":"2011","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib50","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1038\/mt.2012.126","article-title":"Retargeting sleeping beauty transposon insertions by engineered zinc finger DNA-binding domains","volume":"20","author":"Voigt","year":"2012","journal-title":"Mol Ther"},{"key":"10.1038\/mt.2014.131_bib51","doi-asserted-by":"crossref","first-page":"9197","DOI":"10.1093\/nar\/gkt677","article-title":"Transcription activator like effector (TALE)-directed piggyBac transposition in human cells","volume":"41","author":"Owens","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"10.1038\/mt.2014.131_bib52","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature10177","article-title":"In vivo genome editing restores haemostasis in a mouse model of haemophilia","volume":"475","author":"Li","year":"2011","journal-title":"Nature"},{"key":"10.1038\/mt.2014.131_bib53","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nbt.2884","article-title":"Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype","volume":"32","author":"Yin","year":"2014","journal-title":"Nat Biotechnol"},{"key":"10.1038\/mt.2014.131_bib54","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/CJI.0b013e3182811ce9","article-title":"Sleeping beauty system to redirect T-cell specificity for human applications","volume":"36","author":"Maiti","year":"2013","journal-title":"J Immunother"},{"key":"10.1038\/mt.2014.131_bib55","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\/mt.2014.131_bib56","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s004380100525","article-title":"The minimum internal and external sequence requirements for transposition of the eukaryotic transformation vector piggyBac","volume":"266","author":"Li","year":"2001","journal-title":"Mol Genet Genomics"},{"key":"10.1038\/mt.2014.131_bib57","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2583.2004.00525.x","article-title":"piggyBac internal sequences are necessary for efficient transformation of target genomes","volume":"14","author":"Li","year":"2005","journal-title":"Insect Mol Biol"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616307614?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001616307614?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T15:49:15Z","timestamp":1668786555000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001616307614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9]]},"references-count":57,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["S1525001616307614"],"URL":"https:\/\/doi.org\/10.1038\/mt.2014.131","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2014,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hyperactive PiggyBac Transposons for Sustained and Robust Liver-targeted Gene Therapy","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/mt.2014.131","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 American Society of Gene & Cell Therapy. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}