{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:26:38Z","timestamp":1788888398227,"version":"build-2803163510"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS|National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL064274"],"award-info":[{"award-number":["R01 HL064274"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Crigler\u2010Najjar syndrome type I (CNSI) is a rare monogenic disease characterized by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of neurological damage and death. Liver transplantation is the only curative option, which has several limitations and risks. We applied an\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    gene targeting approach based on the insertion, without the use of nucleases, of a promoterless therapeutic cDNA into the albumin locus of a mouse model reproducing all major features of CNSI. Neonatal transduction with the donor vector resulted in the complete rescue from neonatal lethality, with a therapeutic reduction in plasma bilirubin lasting for at least 12\u00a0months, the latest time point analyzed. Mutant mice, which expressed about 5\u20136% of WT Ugt1a1 levels, showed normal liver histology and motor\u2010coordination abilities, suggesting no functional liver or brain abnormalities. These results proved that the promoterless gene therapy is applicable for CNSI, providing therapeutic levels of an intracellular ER membrane\u2010bound enzyme responsible for a lethal liver metabolic disease.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201707601","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T20:30:27Z","timestamp":1501187427000},"page":"1346-1355","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Promoterless gene targeting without nucleases rescues lethality of a Crigler\u2010Najjar syndrome mouse model"],"prefix":"10.1038","volume":"9","author":[{"given":"Fabiola","family":"Porro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bortolussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Barzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"De Caneva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Iaconcig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Vodret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Zentilin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Kay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9628-0494","authenticated-orcid":false,"given":"Andr\u00e9s F","family":"Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"BFEMMM201707601_CR1","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jhep.2012.04.015","volume":"57","author":"R Adam","year":"2012","unstructured":"Adam R, Karam V, Delvart V, O'Grady J, Mirza D, Klempnauer J, Castaing D, Neuhaus P, Jamieson N, Salizzoni M et\u00a0al (2012) Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol 57: 675\u2013688","journal-title":"J Hepatol"},{"key":"BFEMMM201707601_CR2","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1182\/blood-2013-04-497354","volume":"122","author":"XM Anguela","year":"2013","unstructured":"Anguela XM, Sharma R, Doyon Y, Miller JC, Li H, Haurigot V, Rohde ME, Wong SY, Davidson RJ, Zhou S et\u00a0al (2013) Robust ZFN\u2010mediated genome editing in adult hemophilic mice. Blood 122: 3283\u20133287","journal-title":"Blood"},{"key":"BFEMMM201707601_CR3","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/0022-3468(92)90850-7","volume":"27","author":"K Asonuma","year":"1992","unstructured":"Asonuma K, Gilbert JC, Stein JE, Takeda T, Vacanti JP (1992) Quantitation of transplanted hepatic mass necessary to cure the Gunn rat model of hyperbilirubinemia. J Pediatr Surg 27: 298\u2013301","journal-title":"J Pediatr Surg"},{"key":"BFEMMM201707601_CR4","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nature13864","volume":"517","author":"A Barzel","year":"2015","unstructured":"Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector LP, Porteus MH, Gaensler KM et\u00a0al (2015) Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517: 360\u2013364","journal-title":"Nature"},{"key":"BFEMMM201707601_CR5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ymgme.2011.06.002","volume":"104","author":"P Bell","year":"2011","unstructured":"Bell P, Wang L, Gao G, Haskins ME, Tarantal AF, McCarter RJ, Zhu Y, Yu H, Wilson JM (2011) Inverse zonation of hepatocyte transduction with AAV vectors between mice and non\u2010human primates. Mol Genet Metab 104: 395\u2013403","journal-title":"Mol Genet Metab"},{"key":"BFEMMM201707601_CR6","first-page":"145","volume":"26","author":"L Bockor","year":"2017","unstructured":"Bockor L, Bortolussi G, Vodret S, Iaconcig A, Jasprova J, Zelenka J, Vitek L, Tiribelli C, Muro AF (2017) Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1\u2010\/\u2010 lethal mouse model of neonatal hyperbilirubinemia. Hum Mol Genet 26: 145\u2013157","journal-title":"Hum Mol Genet"},{"key":"BFEMMM201707601_CR7","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1096\/fj.11-195461","volume":"26","author":"G Bortolussi","year":"2012","unstructured":"Bortolussi G, Zentilin L, Baj G, Giraudi P, Bellarosa C, Giacca M, Tiribelli C, Muro AF (2012) Rescue of bilirubin\u2010induced neonatal lethality in a mouse model of Crigler\u2010Najjar syndrome type I by AAV9\u2010mediated gene transfer. FASEB J 26: 1052\u20131063","journal-title":"FASEB J"},{"key":"BFEMMM201707601_CR8","first-page":"1057","volume":"7","author":"G Bortolussi","year":"2014","unstructured":"Bortolussi G, Baj G, Vodret S, Viviani G, Bittolo T, Muro AF (2014a) Age\u2010dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in\u00a0vivo. Dis Model Mech 7: 1057\u20131068","journal-title":"Dis Model Mech"},{"key":"BFEMMM201707601_CR9","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1089\/hum.2013.233","volume":"25","author":"G Bortolussi","year":"2014","unstructured":"Bortolussi G, Zentilin L, Vanikova J, Bockor L, Bellarosa C, Mancarella A, Vianello E, Tiribelli C, Giacca M, Vitek L et\u00a0al (2014b) Life\u2010long correction of hyperbilirubinemia with a neonatal liver\u2010specific AAV\u2010mediated gene transfer in a lethal mouse model of Crigler Najjar Syndrome. Hum Gene Ther 25: 844\u2013855","journal-title":"Hum Gene Ther"},{"key":"BFEMMM201707601_CR10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0168-8278(02)00359-8","volume":"38","author":"PJ Bosma","year":"2003","unstructured":"Bosma PJ (2003) Inherited disorders of bilirubin metabolism. J Hepatol 38: 107\u2013117","journal-title":"J Hepatol"},{"key":"BFEMMM201707601_CR11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.bcmd.2013.01.003","volume":"50","author":"G Canu","year":"2013","unstructured":"Canu G, Minucci A, Zuppi C, Capoluongo E (2013) Gilbert and Crigler Najjar syndromes: an update of the UDP\u2010glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood Cells Mol Dis 50: 273\u2013280","journal-title":"Blood Cells Mol Dis"},{"key":"BFEMMM201707601_CR12","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev-biochem-060713-035418","volume":"83","author":"D Carroll","year":"2014","unstructured":"Carroll D (2014) Genome engineering with targetable nucleases. Annu Rev Biochem 83: 409\u2013439","journal-title":"Annu Rev Biochem"},{"key":"BFEMMM201707601_CR13","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1172\/JCI79213","volume":"125","author":"RJ Chandler","year":"2015","unstructured":"Chandler RJ, LaFave MC, Varshney GK, Trivedi NS, Carrillo\u2010Carrasco N, Senac JS, Wu W, Hoffmann V, Elkahloun AG, Burgess SM et\u00a0al (2015) Vector design influences hepatic genotoxicity after adeno\u2010associated virus gene therapy. J Clin Investig 125: 870\u2013880","journal-title":"J Clin Investig"},{"key":"BFEMMM201707601_CR14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1542\/peds.10.2.169","volume":"10","author":"JF Crigler Jr","year":"1952","unstructured":"Crigler JF Jr, Najjar VA (1952) Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10: 169\u2013180","journal-title":"Pediatrics"},{"key":"BFEMMM201707601_CR15","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/mt.2008.72","volume":"16","author":"SC Cunningham","year":"2008","unstructured":"Cunningham SC, Dane AP, Spinoulas A, Logan GJ, Alexander IE (2008) Gene delivery to the juvenile mouse liver using AAV2\/8 vectors. Mol Ther 16: 1081\u20131088","journal-title":"Mol Ther"},{"key":"BFEMMM201707601_CR16","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/gt.2012.67","volume":"20","author":"AP Dane","year":"2013","unstructured":"Dane AP, Wowro SJ, Cunningham SC, Alexander IE (2013) Comparison of gene\u00a0transfer to the murine liver following intraperitoneal and intraportal\u00a0delivery of hepatotropic AAV pseudo\u2010serotypes. Gene Ther 20: 460\u2013464","journal-title":"Gene Ther"},{"key":"BFEMMM201707601_CR17","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.1142658","volume":"317","author":"A Donsante","year":"2007","unstructured":"Donsante A, Miller DG, Li Y, Vogler C, Brunt EM, Russell DW, Sands MS (2007) AAV vector integration sites in mouse hepatocellular carcinoma. Science 317: 477","journal-title":"Science"},{"key":"BFEMMM201707601_CR18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0003-9861(02)00351-X","volume":"405","author":"Y Emi","year":"2002","unstructured":"Emi Y, Omura S, Ikushiro S, Iyanagi T (2002) Accelerated degradation of mislocalized UDP\u2010glucuronosyltransferase family 1 (UGT1) proteins in Gunn rat hepatocytes. Arch Biochem Biophys 405: 163\u2013169","journal-title":"Arch Biochem Biophys"},{"key":"BFEMMM201707601_CR19","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.jhep.2013.04.004","volume":"59","author":"S Fagiuoli","year":"2013","unstructured":"Fagiuoli S, Daina E, D'Antiga L, Colledan M, Remuzzi G (2013) Monogenic diseases that can be cured by liver transplantation. J Hepatol 59: 595\u2013612","journal-title":"J Hepatol"},{"key":"BFEMMM201707601_CR20","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1056\/NEJM199805143382004","volume":"338","author":"IJ Fox","year":"1998","unstructured":"Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (1998) Treatment of the Crigler\u2010Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 338: 1422\u20131426","journal-title":"N Engl J Med"},{"key":"BFEMMM201707601_CR21","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","volume":"31","author":"Y Fu","year":"2013","unstructured":"Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013) High\u2010frequency off\u2010target mutagenesis induced by CRISPR\u2010Cas nucleases in human cells. Nat Biotechnol 31: 822\u2013826","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201707601_CR22","first-page":"536","volume":"90","author":"PW Huang","year":"1970","unstructured":"Huang PW, Rozdilsky B, Gerrard JW, Goluboff N, Holman GH (1970) Crigler\u2010Najjar syndrome in four of five siblings with postmortem findings in one. Arch Pathol 90: 536\u2013539","journal-title":"Arch Pathol"},{"key":"BFEMMM201707601_CR23","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1016\/j.transproceed.2014.07.039","volume":"46","author":"G Immordino","year":"2014","unstructured":"Immordino G, Bottino G, De Negri A, Diviacco P, Moraglia E, Ferrari C, Picciotto A, Andorno E (2014) Predictability and survival in liver replantransplantation: monocentric experience. Transpl Proc 46: 2290\u20132292","journal-title":"Transpl Proc"},{"key":"BFEMMM201707601_CR24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm3486","volume":"14","author":"JK Joung","year":"2013","unstructured":"Joung JK, Sander JD (2013) TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14: 49\u201355","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMMM201707601_CR25","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z","volume":"16","author":"A Kadakol","year":"2000","unstructured":"Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR (2000) Genetic lesions of bilirubin uridine\u2010diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler\u2010Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 16: 297\u2013306","journal-title":"Hum Mutat"},{"key":"BFEMMM201707601_CR26","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nrg2971","volume":"12","author":"MA Kay","year":"2011","unstructured":"Kay MA (2011) State\u2010of\u2010the\u2010art gene\u2010based therapies: the road ahead. Nat Rev Genet 12: 316\u2013328","journal-title":"Nat Rev Genet"},{"key":"BFEMMM201707601_CR27","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nbt.3190","volume":"33","author":"T Maruyama","year":"2015","unstructured":"Maruyama T, Dougan SK, Truttmann MC, Bilate AM, Ingram JR, Ploegh HL (2015) Increasing the efficiency of precise genome editing with CRISPR\u2010Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol 33: 538\u2013542","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201707601_CR28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nrg2988","volume":"12","author":"F Mingozzi","year":"2011","unstructured":"Mingozzi F, High KA (2011) Therapeutic in\u00a0vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 12: 341\u2013355","journal-title":"Nat Rev Genet"},{"key":"BFEMMM201707601_CR29","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jmv.21360","volume":"81","author":"SL Murphy","year":"2009","unstructured":"Murphy SL, Li H, Mingozzi F, Sabatino DE, Hui DJ, Edmonson SA, High KA (2009) Diverse IgG subclass responses to adeno\u2010associated virus infection and vector administration. J Med Virol 81: 65\u201374","journal-title":"J Med Virol"},{"key":"BFEMMM201707601_CR30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/gt.2008.137","volume":"16","author":"AC Nathwani","year":"2009","unstructured":"Nathwani AC, Cochrane M, McIntosh J, Ng CY, Zhou J, Gray JT, Davidoff AM (2009) Enhancing transduction of the liver by adeno\u2010associated viral vectors. Gene Ther 16: 60\u201369","journal-title":"Gene Ther"},{"key":"BFEMMM201707601_CR31","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1056\/NEJMoa1108046","volume":"365","author":"AC Nathwani","year":"2011","unstructured":"Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C et\u00a0al (2011) Adenovirus\u2010associated virus vector\u2010mediated gene transfer in hemophilia B. N Engl J Med 365: 2357\u20132365","journal-title":"N Engl J Med"},{"key":"BFEMMM201707601_CR32","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa1407309","volume":"371","author":"AC Nathwani","year":"2014","unstructured":"Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D et\u00a0al (2014) Long\u2010term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 371: 1994\u20132004","journal-title":"N Engl J Med"},{"key":"BFEMMM201707601_CR33","doi-asserted-by":"crossref","first-page":"342ra379","DOI":"10.1126\/scitranslmed.aad8166","volume":"8","author":"S Nygaard","year":"2016","unstructured":"Nygaard S, Barzel A, Haft A, Major A, Finegold M, Kay MA, Grompe M (2016) A universal system to select gene\u2010modified hepatocytes in\u00a0vivo. Sci Transl Med 8: 342ra379","journal-title":"Sci Transl Med"},{"key":"BFEMMM201707601_CR34","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1089\/hum.2012.038","volume":"23","author":"NK Paulk","year":"2012","unstructured":"Paulk NK, Loza LM, Finegold MJ, Grompe M (2012) AAV\u2010mediated gene targeting is significantly enhanced by transient inhibition of nonhomologous end joining or the proteasome in\u00a0vivo. Hum Gene Ther 23: 658\u2013665","journal-title":"Hum Gene Ther"},{"key":"BFEMMM201707601_CR35","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1101\/gad.1.3.268","volume":"1","author":"CA Pinkert","year":"1987","unstructured":"Pinkert CA, Ornitz DM, Brinster RL, Palmiter RD (1987) An albumin enhancer located 10\u00a0kb upstream functions along with its promoter to direct efficient, liver\u2010specific expression in transgenic mice. Genes Dev 1: 268\u2013276","journal-title":"Genes Dev"},{"key":"BFEMMM201707601_CR36","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1083\/jcb.103.3.777","volume":"103","author":"AM Poliard","year":"1986","unstructured":"Poliard AM, Bernuau D, Tournier I, Legres LG, Schoevaert D, Feldmann G, Sala\u2010Trepat JM (1986) Cellular analysis by in\u00a0situ hybridization and immunoperoxidase of alpha\u2010fetoprotein and albumin gene expression in rat liver during the perinatal period. J Cell Biol 103: 777\u2013786","journal-title":"J Cell Biol"},{"key":"BFEMMM201707601_CR37","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/sj.gt.3302766","volume":"13","author":"C Riviere","year":"2006","unstructured":"Riviere C, Danos O, Douar AM (2006) Long\u2010term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice. Gene Ther 13: 1300\u20131308","journal-title":"Gene Ther"},{"key":"BFEMMM201707601_CR38","doi-asserted-by":"crossref","first-page":"16049","DOI":"10.1038\/mtm.2016.49","volume":"3","author":"G Ronzitti","year":"2016","unstructured":"Ronzitti G, Bortolussi G, van Dijk R, Collaud F, Charles S, Leborgne C, Vidal P, Martin S, Gjata B, Sola MS et\u00a0al (2016) A translationally optimized AAV\u2010UGT1A1 vector drives safe and long\u2010lasting correction of Crigler\u2010Najjar syndrome. Mol Ther Methods Clin Dev 3:  16049","journal-title":"Mol Ther Methods Clin Dev"},{"key":"BFEMMM201707601_CR39","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/ng0498-325","volume":"18","author":"DW Russell","year":"1998","unstructured":"Russell DW, Hirata RK (1998) Human gene targeting by viral vectors. Nat Genet 18: 325\u2013330","journal-title":"Nat Genet"},{"key":"BFEMMM201707601_CR40","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1182\/blood-2014-12-615492","volume":"126","author":"R Sharma","year":"2015","unstructured":"Sharma R, Anguela XM, Doyon Y, Wechsler T, DeKelver RC, Sproul S, Paschon DE, Miller JC, Davidson RJ, Shivak D et\u00a0al (2015) In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood 126: 1777\u20131784","journal-title":"Blood"},{"key":"BFEMMM201707601_CR41","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/humu.21133","volume":"31","author":"N Sneitz","year":"2010","unstructured":"Sneitz N, Bakker CT, de Knegt RJ, Halley DJ, Finel M, Bosma PJ (2010) Crigler\u2010Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype\u2010phenotype correlation, and functional analysis of 10 missense mutants. Hum Mutat 31: 52\u201359","journal-title":"Hum Mutat"},{"key":"BFEMMM201707601_CR42","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1016\/j.cell.2012.11.054","volume":"151","author":"M Srivastava","year":"2012","unstructured":"Srivastava M, Nambiar M, Sharma S, Karki SS, Goldsmith G, Hegde M, Kumar S, Pandey M, Singh RK, Ray P et\u00a0al (2012) An inhibitor of nonhomologous end\u2010joining abrogates double\u2010strand break repair and impedes cancer progression. Cell 151: 1474\u20131487","journal-title":"Cell"},{"key":"BFEMMM201707601_CR43","doi-asserted-by":"crossref","first-page":"5254","DOI":"10.1073\/pnas.79.17.5254","volume":"79","author":"SM Tilghman","year":"1982","unstructured":"Tilghman SM, Belayew A (1982) Transcriptional control of the murine albumin\/alpha\u2010fetoprotein locus during development. Proc Natl Acad Sci USA 79: 5254\u20135257","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201707601_CR44","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nrg2842","volume":"11","author":"FD Urnov","year":"2010","unstructured":"Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11: 636\u2013646","journal-title":"Nat Rev Genet"},{"key":"BFEMMM201707601_CR45","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1038\/mt.2012.220","volume":"20","author":"PN Valdmanis","year":"2012","unstructured":"Valdmanis PN, Lisowski L, Kay MA (2012) rAAV\u2010mediated tumorigenesis: still unresolved after an AAV assault. Mol Ther 20: 2014\u20132017","journal-title":"Mol Ther"},{"key":"BFEMMM201707601_CR46","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12974-017-0838-1","volume":"14","author":"S Vodret","year":"2017","unstructured":"Vodret S, Bortolussi G, Jasprova J, Vitek L, Muro AF (2017) Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1\u2212\/\u2212 mouse model. J Neuroinflammation 14: 64","journal-title":"J Neuroinflammation"},{"key":"BFEMMM201707601_CR47","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/hum.2011.183","volume":"23","author":"L Wang","year":"2012","unstructured":"Wang L, Wang H, Bell P, McMenamin D, Wilson JM (2012) Hepatic gene transfer in neonatal mice by adeno\u2010associated virus serotype 8 vector. Hum Gene Ther 23: 533\u2013539","journal-title":"Hum Gene Ther"},{"key":"BFEMMM201707601_CR48","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-biochem-060815-014607","volume":"85","author":"H Wang","year":"2016","unstructured":"Wang H, La Russa M, Qi LS (2016) CRISPR\/Cas9 in genome editing and beyond. Annu Rev Biochem 85: 227\u2013264","journal-title":"Annu Rev Biochem"},{"key":"BFEMMM201707601_CR49","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nbt.3469","volume":"34","author":"Y Yang","year":"2016","unstructured":"Yang Y, Wang L, Bell P, McMenamin D, He Z, White J, Yu H, Xu C, Morizono H, Musunuru K et\u00a0al (2016) A dual AAV system enables the Cas9\u2010mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol 34: 334\u2013338","journal-title":"Nat Biotechnol"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201707601.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.201707601","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.201707601\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.201707601","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.201707601.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:21:41Z","timestamp":1779085301000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.201707601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,27]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10,1]]}},"alternative-id":["BFEMMM201707601"],"URL":"https:\/\/doi.org\/10.15252\/emmm.201707601","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,27]]},"assertion":[{"value":"24 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.A.K. and A.B. are shareholders for LogicBio Therapeutics that has licensed the GeneRide technology from Stanford University.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}