Skip to main content
Top
Published in: Clinical Reviews in Allergy & Immunology 2-3/2015

01-06-2015

Gene Replacement Therapy for Genetic Hepatocellular Jaundice

Authors: Remco van Dijk, Ulrich Beuers, Piter J. Bosma

Published in: Clinical Reviews in Allergy & Immunology | Issue 2-3/2015

Login to get access

Abstract

Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.
Literature
1.
go back to reference Bissell DM (1975) Formation and elimination of bilirubin. Gastroenterology 69:519–538PubMed Bissell DM (1975) Formation and elimination of bilirubin. Gastroenterology 69:519–538PubMed
3.
go back to reference Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 61:748–755PubMedCentralPubMedCrossRef Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 61:748–755PubMedCentralPubMedCrossRef
4.
go back to reference Tenhunen R, Marver HS, Schmid R (1970) The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin. J Lab Clin Med 75:410–421PubMed Tenhunen R, Marver HS, Schmid R (1970) The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin. J Lab Clin Med 75:410–421PubMed
5.
go back to reference Tenhunen R, Ross ME, Marver HS, Schmid R (1970) Reduced nicotinamide-adenine dinucleotide phosphate dependent biliverdin reductase: partial purification and characterization. Biochemistry 9:298–303, 20-1PubMedCrossRef Tenhunen R, Ross ME, Marver HS, Schmid R (1970) Reduced nicotinamide-adenine dinucleotide phosphate dependent biliverdin reductase: partial purification and characterization. Biochemistry 9:298–303, 20-1PubMedCrossRef
6.
go back to reference Sorrentino D, Berk PD (1988) Mechanistic aspects of hepatic bilirubin uptake. Semin Liver Dis 8:119–136PubMedCrossRef Sorrentino D, Berk PD (1988) Mechanistic aspects of hepatic bilirubin uptake. Semin Liver Dis 8:119–136PubMedCrossRef
7.
go back to reference Tiribelli C, Ostrow JD (1993) New concepts in bilirubin chemistry, transport and metabolism: report of the Second International Bilirubin Workshop, April 9–11, 1992, Trieste, Italy. Hepatology 17:715–736PubMedCrossRef Tiribelli C, Ostrow JD (1993) New concepts in bilirubin chemistry, transport and metabolism: report of the Second International Bilirubin Workshop, April 9–11, 1992, Trieste, Italy. Hepatology 17:715–736PubMedCrossRef
8.
9.
go back to reference Dubin IN, Johnson FB (1954) Chronic idiopathic jaundice with unidentified pigment in liver cells; a new clinicopathologic entity with a report of 12 cases. Medicine (Baltimore) 33:155–197CrossRef Dubin IN, Johnson FB (1954) Chronic idiopathic jaundice with unidentified pigment in liver cells; a new clinicopathologic entity with a report of 12 cases. Medicine (Baltimore) 33:155–197CrossRef
10.
go back to reference Sprinz H, Nelson RS (1954) Persistent non-hemolytic hyperbilirubinemia associated with lipochrome-like pigment in liver cells: report of four cases. Ann Intern Med 41:952–962PubMedCrossRef Sprinz H, Nelson RS (1954) Persistent non-hemolytic hyperbilirubinemia associated with lipochrome-like pigment in liver cells: report of four cases. Ann Intern Med 41:952–962PubMedCrossRef
11.
go back to reference Swartz HM, Sarna T, Varma RR (1979) On the natural and excretion of the hepatic pigment in the Dubin-Johnson syndrome. Gastroenterology 76:958–964PubMed Swartz HM, Sarna T, Varma RR (1979) On the natural and excretion of the hepatic pigment in the Dubin-Johnson syndrome. Gastroenterology 76:958–964PubMed
12.
go back to reference Koskelo P, Toivonen I, Adlercreutz H (1967) Urinary coproporphyrin isomer distribution in the Dubin-Johnson syndrome. Clin Chem 13:1006–1009PubMed Koskelo P, Toivonen I, Adlercreutz H (1967) Urinary coproporphyrin isomer distribution in the Dubin-Johnson syndrome. Clin Chem 13:1006–1009PubMed
13.
go back to reference Kondo T, Kuchiba K, Shimizu Y (1976) Coproporphyrin isomers in Dubin-Johnson syndrome. Gastroenterology 70:1117–1120PubMed Kondo T, Kuchiba K, Shimizu Y (1976) Coproporphyrin isomers in Dubin-Johnson syndrome. Gastroenterology 70:1117–1120PubMed
14.
go back to reference Paulusma CC, Bosma PJ, Zaman GJ, Bakker CT, Otter M, Scheffer GL, Scheper RJ, Borst P, Oude Elferink RP (1996) Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271:1126–1128PubMedCrossRef Paulusma CC, Bosma PJ, Zaman GJ, Bakker CT, Otter M, Scheffer GL, Scheper RJ, Borst P, Oude Elferink RP (1996) Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271:1126–1128PubMedCrossRef
15.
go back to reference Paulusma CC, Kool M, Bosma PJ, Scheffer GL, Ter BF, Scheper RJ, Tytgat GN, Borst P, Baas F, Oude Elferink RP (1997) A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology 25:1539–1542PubMedCrossRef Paulusma CC, Kool M, Bosma PJ, Scheffer GL, Ter BF, Scheper RJ, Tytgat GN, Borst P, Baas F, Oude Elferink RP (1997) A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology 25:1539–1542PubMedCrossRef
16.
go back to reference Keppler D, Konig J, Buchler M (1997) The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv Enzyme Regul 37:321–333PubMedCrossRef Keppler D, Konig J, Buchler M (1997) The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv Enzyme Regul 37:321–333PubMedCrossRef
17.
go back to reference Miller DS, Nobmann SN, Gutmann H, Toeroek M, Drewe J, Fricker G (2000) Xenobiotic transport across isolated brain microvessels studied by confocal microscopy. Mol Pharmacol 58:1357–1367PubMed Miller DS, Nobmann SN, Gutmann H, Toeroek M, Drewe J, Fricker G (2000) Xenobiotic transport across isolated brain microvessels studied by confocal microscopy. Mol Pharmacol 58:1357–1367PubMed
18.
go back to reference Borst P, Zelcer N, van de Wetering K (2006) MRP2 and 3 in health and disease. Cancer Lett 234:51–61PubMedCrossRef Borst P, Zelcer N, van de Wetering K (2006) MRP2 and 3 in health and disease. Cancer Lett 234:51–61PubMedCrossRef
19.
go back to reference Jedlitschky G, Hoffmann U, Kroemer HK (2006) Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin Drug Metab Toxicol 2:351–366PubMedCrossRef Jedlitschky G, Hoffmann U, Kroemer HK (2006) Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin Drug Metab Toxicol 2:351–366PubMedCrossRef
21.
go back to reference Rotor AB, Manahan L, Florentin A (1948) Familial nonhemolytic jaundice with direct van den Bergh reaction. Acta Med Phil 5:37–49 Rotor AB, Manahan L, Florentin A (1948) Familial nonhemolytic jaundice with direct van den Bergh reaction. Acta Med Phil 5:37–49
22.
go back to reference Shimizu Y, Naruto H, Ida S, Kohakura M (1981) Urinary coproporphyrin isomers in Rotor’s syndrome: a study in eight families. Hepatology 1:173–178PubMedCrossRef Shimizu Y, Naruto H, Ida S, Kohakura M (1981) Urinary coproporphyrin isomers in Rotor’s syndrome: a study in eight families. Hepatology 1:173–178PubMedCrossRef
23.
go back to reference Wolpert E, Pascasio FM, Wolkoff AW, Arias IM (1977) Abnormal sulfobromophthalein metabolism in Rotor’s syndrome and obligate heterozygotes. N Engl J Med 296:1099–1101PubMedCrossRef Wolpert E, Pascasio FM, Wolkoff AW, Arias IM (1977) Abnormal sulfobromophthalein metabolism in Rotor’s syndrome and obligate heterozygotes. N Engl J Med 296:1099–1101PubMedCrossRef
24.
go back to reference van de Steeg E, Stranecky V, Hartmannova H, Noskova L, Hrebicek M, Wagenaar E, van Esch A, de Waart DR, Oude Elferink RP, Kenworthy KE, Sticova E, Al-Edreesi M, Knisely AS, Kmoch S, Jirsa M, Schinkel AH (2012) Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 122:519–528PubMedCentralPubMedCrossRef van de Steeg E, Stranecky V, Hartmannova H, Noskova L, Hrebicek M, Wagenaar E, van Esch A, de Waart DR, Oude Elferink RP, Kenworthy KE, Sticova E, Al-Edreesi M, Knisely AS, Kmoch S, Jirsa M, Schinkel AH (2012) Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 122:519–528PubMedCentralPubMedCrossRef
25.
go back to reference Hagenbuch B, Gui C (2008) Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 38:778–801PubMedCrossRef Hagenbuch B, Gui C (2008) Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 38:778–801PubMedCrossRef
26.
go back to reference Konig J, Cui Y, Nies AT, Keppler D (2000) Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J Biol Chem 275:23161–23168PubMedCrossRef Konig J, Cui Y, Nies AT, Keppler D (2000) Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J Biol Chem 275:23161–23168PubMedCrossRef
27.
go back to reference Crigler JF Jr, Najjar VA (1952) Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10:169–180PubMed Crigler JF Jr, Najjar VA (1952) Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10:169–180PubMed
28.
go back to reference Sinaasappel M, Jansen PL (1991) The differential diagnosis of Crigler-Najjar disease, types 1 and 2, by bile pigment analysis. Gastroenterology 100:783–789PubMed Sinaasappel M, Jansen PL (1991) The differential diagnosis of Crigler-Najjar disease, types 1 and 2, by bile pigment analysis. Gastroenterology 100:783–789PubMed
29.
go back to reference Arias IM, Gartner LM, Cohen M, Ezzer JB, Levi AJ (1969) Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med 47:395–409PubMedCrossRef Arias IM, Gartner LM, Cohen M, Ezzer JB, Levi AJ (1969) Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med 47:395–409PubMedCrossRef
30.
go back to reference Ritter JK, Crawford JM, Owens IS (1991) Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol Chem 266:1043–1047PubMed Ritter JK, Crawford JM, Owens IS (1991) Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol Chem 266:1043–1047PubMed
31.
go back to reference Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS (1992) A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem 267:3257–3261PubMed Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS (1992) A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem 267:3257–3261PubMed
32.
go back to reference Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC (2001) Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Pharmacogenetics 11:357–368PubMedCrossRef Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC (2001) Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Pharmacogenetics 11:357–368PubMedCrossRef
33.
go back to reference Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR, Chowdhury NR, Jansen PL (1994) Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 269:17960–17964PubMed Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR, Chowdhury NR, Jansen PL (1994) Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 269:17960–17964PubMed
34.
go back to reference Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O (1993) Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun 197:1239–1244PubMedCrossRef Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O (1993) Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun 197:1239–1244PubMedCrossRef
35.
go back to reference Ritter JK, Yeatman MT, Ferreira P, Owens IS (1992) Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient. J Clin Invest 90:150–155PubMedCentralPubMedCrossRef Ritter JK, Yeatman MT, Ferreira P, Owens IS (1992) Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient. J Clin Invest 90:150–155PubMedCentralPubMedCrossRef
36.
go back to reference Bosma PJ, Chowdhury NR, Goldhoorn BG, Hofker MH, Oude Elferink RP, Jansen PL, Chowdhury JR (1992) Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology 15:941–947PubMedCrossRef Bosma PJ, Chowdhury NR, Goldhoorn BG, Hofker MH, Oude Elferink RP, Jansen PL, Chowdhury JR (1992) Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology 15:941–947PubMedCrossRef
37.
go back to reference Canu G, Minucci A, Zuppi C, Capoluongo E (2013) Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood Cells Mol Dis 50:273–280PubMedCrossRef Canu G, Minucci A, Zuppi C, Capoluongo E (2013) Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood Cells Mol Dis 50:273–280PubMedCrossRef
38.
go back to reference Meulengracht E (1947) A review of chronic intermittent juvenile jaundice. Q J Med 16:83–98PubMed Meulengracht E (1947) A review of chronic intermittent juvenile jaundice. Q J Med 16:83–98PubMed
39.
go back to reference Gilbert ALP (1901) La cholamae simple familiale. Sem Med 21:241 Gilbert ALP (1901) La cholamae simple familiale. Sem Med 21:241
40.
go back to reference Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333:1171–1175PubMedCrossRef Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333:1171–1175PubMedCrossRef
41.
go back to reference Raijmakers MT, Jansen PL, Steegers EA, Peters WH (2000) Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 33:348–351PubMedCrossRef Raijmakers MT, Jansen PL, Steegers EA, Peters WH (2000) Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 33:348–351PubMedCrossRef
42.
go back to reference Black M, Billing BH (1968) ‘In vitro’ assay of bilirubin-UDP glucuronyl transferase activity in the liver of patients with Gilbert’s syndrome and a variety of hepatic disorders. Gut 9:728–729PubMed Black M, Billing BH (1968) ‘In vitro’ assay of bilirubin-UDP glucuronyl transferase activity in the liver of patients with Gilbert’s syndrome and a variety of hepatic disorders. Gut 9:728–729PubMed
43.
go back to reference Black M, Billing BH (1969) Hepatic bilirubin UDP-glucuronyl transferase activity in liver disease and Gilbert’s syndrome. N Engl J Med 280:1266–1271PubMedCrossRef Black M, Billing BH (1969) Hepatic bilirubin UDP-glucuronyl transferase activity in liver disease and Gilbert’s syndrome. N Engl J Med 280:1266–1271PubMedCrossRef
44.
go back to reference Monaghan G, Ryan M, Seddon R, Hume R, Burchell B (1996) Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 347:578–581PubMedCrossRef Monaghan G, Ryan M, Seddon R, Hume R, Burchell B (1996) Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 347:578–581PubMedCrossRef
45.
go back to reference Hall D, Ybazeta G, Destro-Bisol G, Petzl-Erler ML, Di RA (1999) Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 9:591–599PubMedCrossRef Hall D, Ybazeta G, Destro-Bisol G, Petzl-Erler ML, Di RA (1999) Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 9:591–599PubMedCrossRef
46.
47.
go back to reference Soeda Y, Yamamoto K, Adachi Y, Hori T, Aono S, Koiwai O, Sato H (1995) Predicted homozygous mis-sense mutation in Gilbert’s syndrome. Lancet 346:1494PubMedCrossRef Soeda Y, Yamamoto K, Adachi Y, Hori T, Aono S, Koiwai O, Sato H (1995) Predicted homozygous mis-sense mutation in Gilbert’s syndrome. Lancet 346:1494PubMedCrossRef
48.
49.
go back to reference Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S (2004) Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos 32:314–320PubMedCrossRef Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S (2004) Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos 32:314–320PubMedCrossRef
50.
go back to reference Ebner T, Remmel RP, Burchell B (1993) Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol 43:649–654PubMed Ebner T, Remmel RP, Burchell B (1993) Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol Pharmacol 43:649–654PubMed
51.
go back to reference McGill MR, Jaeschke H (2013) Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res 30:2174–2187PubMedCentralPubMedCrossRef McGill MR, Jaeschke H (2013) Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res 30:2174–2187PubMedCentralPubMedCrossRef
52.
go back to reference Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, Pearson PG, Baillie TA (2002) Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 30:505–512PubMedCrossRef Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, Pearson PG, Baillie TA (2002) Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 30:505–512PubMedCrossRef
53.
go back to reference Tukey RH, Strassburg CP, Mackenzie PI (2002) Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol Pharmacol 62:446–450PubMedCrossRef Tukey RH, Strassburg CP, Mackenzie PI (2002) Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol Pharmacol 62:446–450PubMedCrossRef
54.
go back to reference Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382–1388PubMedCrossRef Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382–1388PubMedCrossRef
55.
go back to reference Innocenti F, Ratain MJ (2003) Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology (Williston Park) 17:52–55PubMed Innocenti F, Ratain MJ (2003) Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology (Williston Park) 17:52–55PubMed
56.
go back to reference Zucker SD, Qin X, Rouster SD, Yu F, Green RM, Keshavan P, Feinberg J, Sherman KE (2001) Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci U S A 98:12671–12676PubMedCentralPubMedCrossRef Zucker SD, Qin X, Rouster SD, Yu F, Green RM, Keshavan P, Feinberg J, Sherman KE (2001) Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci U S A 98:12671–12676PubMedCentralPubMedCrossRef
57.
go back to reference Lankisch TO, Behrens G, Ehmer U, Mobius U, Rockstroh J, Wehmeier M, Kalthoff S, Freiberg N, Manns MP, Schmidt RE, Strassburg CP (2009) Gilbert’s syndrome and hyperbilirubinemia in protease inhibitor therapy—an extended haplotype of genetic variants increases risk in indinavir treatment. J Hepatol 50:1010–1018PubMedCrossRef Lankisch TO, Behrens G, Ehmer U, Mobius U, Rockstroh J, Wehmeier M, Kalthoff S, Freiberg N, Manns MP, Schmidt RE, Strassburg CP (2009) Gilbert’s syndrome and hyperbilirubinemia in protease inhibitor therapy—an extended haplotype of genetic variants increases risk in indinavir treatment. J Hepatol 50:1010–1018PubMedCrossRef
58.
go back to reference Shapiro SM, Bhutani VK, Johnson L (2006) Hyperbilirubinemia and kernicterus. Clin Perinatol 33:387–410PubMedCrossRef Shapiro SM, Bhutani VK, Johnson L (2006) Hyperbilirubinemia and kernicterus. Clin Perinatol 33:387–410PubMedCrossRef
59.
go back to reference Watchko JF, Tiribelli C (2013) Bilirubin-induced neurologic damage—mechanisms and management approaches. N Engl J Med 369:2021–2030PubMedCrossRef Watchko JF, Tiribelli C (2013) Bilirubin-induced neurologic damage—mechanisms and management approaches. N Engl J Med 369:2021–2030PubMedCrossRef
60.
go back to reference Poddar B, Bharti B, Goraya J, Parmar VR (2002) Kernicterus in a child with Crigler-Najjar syndrome type II. Trop Gastroenterol 23:33–34PubMed Poddar B, Bharti B, Goraya J, Parmar VR (2002) Kernicterus in a child with Crigler-Najjar syndrome type II. Trop Gastroenterol 23:33–34PubMed
61.
go back to reference Cremer RJ, Perryman PW, Richards DH (1958) Influence of light on the hyperbilirubinaemia of infants. Lancet 1:1094–1097PubMedCrossRef Cremer RJ, Perryman PW, Richards DH (1958) Influence of light on the hyperbilirubinaemia of infants. Lancet 1:1094–1097PubMedCrossRef
62.
go back to reference Ennever JF (1990) Blue light, green light, white light, more light: treatment of neonatal jaundice. Clin Perinatol 17:467–481PubMed Ennever JF (1990) Blue light, green light, white light, more light: treatment of neonatal jaundice. Clin Perinatol 17:467–481PubMed
63.
go back to reference Zenone EA, Stoll MS, Ostrow JD (1982) The effect of elimination of environmental light on the metabolism of unconjugated bilirubin in the Gunn rat. Dig Dis Sci 27:1117–1120PubMedCrossRef Zenone EA, Stoll MS, Ostrow JD (1982) The effect of elimination of environmental light on the metabolism of unconjugated bilirubin in the Gunn rat. Dig Dis Sci 27:1117–1120PubMedCrossRef
64.
go back to reference Stoll MS, Zenone EA, Ostrow JD (1981) Excretion of administered and endogenous photobilirubins in the bile of the jaundice Gunn rat. J Clin Invest 68:134–141PubMedCentralPubMedCrossRef Stoll MS, Zenone EA, Ostrow JD (1981) Excretion of administered and endogenous photobilirubins in the bile of the jaundice Gunn rat. J Clin Invest 68:134–141PubMedCentralPubMedCrossRef
65.
go back to reference Van Der Veere CN, Sinaasappel M, McDonagh AF, Rosenthal P, Labrune P, Odievre M, Fevery J, Otte JB, McClean P, Burk G, Masakowski V, Sperl W, Mowat AP, Vergani GM, Heller K, Wilson JP, Shepherd R, Jansen PL (1996) Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology 24:311–315PubMedCrossRef Van Der Veere CN, Sinaasappel M, McDonagh AF, Rosenthal P, Labrune P, Odievre M, Fevery J, Otte JB, McClean P, Burk G, Masakowski V, Sperl W, Mowat AP, Vergani GM, Heller K, Wilson JP, Shepherd R, Jansen PL (1996) Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology 24:311–315PubMedCrossRef
66.
go back to reference Van Der Veere CN, Schoemaker B, Bakker C, Van Der Meer R, Jansen PL, Elferink RP (1996) Influence of dietary calcium phosphate on the disposition of bilirubin in rats with unconjugated hyperbilirubinemia. Hepatology 24:620–626CrossRef Van Der Veere CN, Schoemaker B, Bakker C, Van Der Meer R, Jansen PL, Elferink RP (1996) Influence of dietary calcium phosphate on the disposition of bilirubin in rats with unconjugated hyperbilirubinemia. Hepatology 24:620–626CrossRef
67.
go back to reference Stoll MS (1986) Phototherapy of jaundice. In: Ostrow JD (ed) Bile pigments and jaundice. Raven, New York, pp 551–580 Stoll MS (1986) Phototherapy of jaundice. In: Ostrow JD (ed) Bile pigments and jaundice. Raven, New York, pp 551–580
69.
go back to reference Strauss KA, Robinson DL, Vreman HJ, Puffenberger EG, Hart G, Morton DH (2006) Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease. Eur J Pediatr 165:306–319PubMedCrossRef Strauss KA, Robinson DL, Vreman HJ, Puffenberger EG, Hart G, Morton DH (2006) Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease. Eur J Pediatr 165:306–319PubMedCrossRef
70.
go back to reference Muiesan P, Vergani D, Mieli-Vergani G (2007) Liver transplantation in children. J Hepatol 46:340–348PubMedCrossRef Muiesan P, Vergani D, Mieli-Vergani G (2007) Liver transplantation in children. J Hepatol 46:340–348PubMedCrossRef
71.
go back to reference Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (1998) Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 338:1422–1426PubMedCrossRef Fox IJ, Chowdhury JR, Kaufman SS, Goertzen TC, Chowdhury NR, Warkentin PI, Dorko K, Sauter BV, Strom SC (1998) Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 338:1422–1426PubMedCrossRef
72.
go back to reference Ambrosino G, Varotto S, Strom SC, Guariso G, Franchin E, Miotto D, Caenazzo L, Basso S, Carraro P, Valente ML, D’Amico D, Zancan L, D’Antiga L (2005) Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant 14:151–157PubMedCrossRef Ambrosino G, Varotto S, Strom SC, Guariso G, Franchin E, Miotto D, Caenazzo L, Basso S, Carraro P, Valente ML, D’Amico D, Zancan L, D’Antiga L (2005) Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant 14:151–157PubMedCrossRef
73.
go back to reference Lysy PA, Najimi M, Stephenne X, Bourgois A, Smets F, Sokal EM (2008) Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives. World J Gastroenterol 14:3464–3470PubMedCentralPubMedCrossRef Lysy PA, Najimi M, Stephenne X, Bourgois A, Smets F, Sokal EM (2008) Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives. World J Gastroenterol 14:3464–3470PubMedCentralPubMedCrossRef
75.
go back to reference Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, Shearer G, Chang L, Chiang Y, Tolstoshev P, Greenblatt JJ, Rosenberg SA, Klein H, Berger M, Mullen CA, Ramsey WJ, Muul L, Morgan RA, Anderson WF (1995) T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years. Science 270:475–480PubMedCrossRef Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, Shearer G, Chang L, Chiang Y, Tolstoshev P, Greenblatt JJ, Rosenberg SA, Klein H, Berger M, Mullen CA, Ramsey WJ, Muul L, Morgan RA, Anderson WF (1995) T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years. Science 270:475–480PubMedCrossRef
76.
go back to reference Gaspar HB, Thrasher AJ (2005) Gene therapy for severe combined immunodeficiencies. Expert Opin Biol Ther 5:1175–1182PubMedCrossRef Gaspar HB, Thrasher AJ (2005) Gene therapy for severe combined immunodeficiencies. Expert Opin Biol Ther 5:1175–1182PubMedCrossRef
77.
go back to reference Cavazzana-Calvo M, Fischer A, Hacein-Bey-Abina S, Aiuti A (2012) Gene therapy for primary immunodeficiencies: part 1. Curr Opin Immunol 24:580–584PubMedCrossRef Cavazzana-Calvo M, Fischer A, Hacein-Bey-Abina S, Aiuti A (2012) Gene therapy for primary immunodeficiencies: part 1. Curr Opin Immunol 24:580–584PubMedCrossRef
78.
go back to reference van der Putten H, Quint W, van Raaij J, Maandag ER, Verma IM, Berns A (1981) M-MuLV-induced leukemogenesis: integration and structure of recombinant proviruses in tumors. Cell 24:729–739PubMedCrossRef van der Putten H, Quint W, van Raaij J, Maandag ER, Verma IM, Berns A (1981) M-MuLV-induced leukemogenesis: integration and structure of recombinant proviruses in tumors. Cell 24:729–739PubMedCrossRef
79.
go back to reference Cavazza A, Moiani A, Mavilio F (2013) Mechanisms of retroviral integration and mutagenesis. Hum Gene Ther 24:119–131PubMedCrossRef Cavazza A, Moiani A, Mavilio F (2013) Mechanisms of retroviral integration and mutagenesis. Hum Gene Ther 24:119–131PubMedCrossRef
80.
go back to reference Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, Ranzani M, Benedicenti F, Sergi LS, Ambrosi A, Ponzoni M, Doglioni C, Di Serio C, von Kalle C, Naldini L (2009) The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J Clin Invest 119:964–975PubMedCentralPubMedCrossRef Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, Ranzani M, Benedicenti F, Sergi LS, Ambrosi A, Ponzoni M, Doglioni C, Di Serio C, von Kalle C, Naldini L (2009) The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J Clin Invest 119:964–975PubMedCentralPubMedCrossRef
82.
go back to reference Peng Z (2005) Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum Gene Ther 16:1016–1027PubMedCrossRef Peng Z (2005) Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum Gene Ther 16:1016–1027PubMedCrossRef
83.
go back to reference Wilson JM (2005) Gendicine: the first commercial gene therapy product. Hum Gene Ther 16:1014–1015PubMedCrossRef Wilson JM (2005) Gendicine: the first commercial gene therapy product. Hum Gene Ther 16:1014–1015PubMedCrossRef
85.
go back to reference Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci U S A 55:1467–1474PubMedCentralPubMedCrossRef Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci U S A 55:1467–1474PubMedCentralPubMedCrossRef
86.
go back to reference Schnepp BC, Jensen RL, Chen CL, Johnson PR, Clark KR (2005) Characterization of adeno-associated virus genomes isolated from human tissues. J Virol 79:14793–14803PubMedCentralPubMedCrossRef Schnepp BC, Jensen RL, Chen CL, Johnson PR, Clark KR (2005) Characterization of adeno-associated virus genomes isolated from human tissues. J Virol 79:14793–14803PubMedCentralPubMedCrossRef
87.
go back to reference Gaudet D, de Wal J, Tremblay K, Dery S, van Deventer S, Freidig A, Brisson D, Methot J (2010) Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency. Atheroscler Suppl 11:55–60PubMedCrossRef Gaudet D, de Wal J, Tremblay K, Dery S, van Deventer S, Freidig A, Brisson D, Methot J (2010) Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency. Atheroscler Suppl 11:55–60PubMedCrossRef
89.
go back to reference Gao G, Vandenberghe LH, Wilson JM (2005) New recombinant serotypes of AAV vectors. Curr Gene Ther 5:285–297PubMedCrossRef Gao G, Vandenberghe LH, Wilson JM (2005) New recombinant serotypes of AAV vectors. Curr Gene Ther 5:285–297PubMedCrossRef
90.
91.
go back to reference Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, O’Beirne J, Smith K, Pasi J, Glader B, Rustagi P, Ng CY, Kay MA, Zhou J, Spence Y, Morton CL, Allay J, Coleman J, Sleep S, Cunningham JM, Srivastava D, Basner-Tschakarjan E, Mingozzi F, High KA, Gray JT, Reiss UM, Nienhuis AW, Davidoff AM (2011) Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 365:2357–2365PubMedCentralPubMedCrossRef Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, O’Beirne J, Smith K, Pasi J, Glader B, Rustagi P, Ng CY, Kay MA, Zhou J, Spence Y, Morton CL, Allay J, Coleman J, Sleep S, Cunningham JM, Srivastava D, Basner-Tschakarjan E, Mingozzi F, High KA, Gray JT, Reiss UM, Nienhuis AW, Davidoff AM (2011) Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 365:2357–2365PubMedCentralPubMedCrossRef
92.
go back to reference Miranda PS, Bosma PJ (2009) Towards liver-directed gene therapy for Crigler-Najjar syndrome. Curr Gene Ther 9:72–82PubMedCrossRef Miranda PS, Bosma PJ (2009) Towards liver-directed gene therapy for Crigler-Najjar syndrome. Curr Gene Ther 9:72–82PubMedCrossRef
94.
95.
go back to reference Chowdhury NR, Arias IM, Lederstein M, Chowdhury JR (1986) Substrates and products of purified rat liver bilirubin UDP-glucuronosyltransferase. Hepatology 6:123–128PubMedCrossRef Chowdhury NR, Arias IM, Lederstein M, Chowdhury JR (1986) Substrates and products of purified rat liver bilirubin UDP-glucuronosyltransferase. Hepatology 6:123–128PubMedCrossRef
96.
go back to reference Tada K, Roy-Chowdhury N, Prasad V, Kim BH, Manchikalapudi P, Fox IJ, van Duijvendijk P, Bosma PJ, Roy-Chowdhury J (1998) Long-term amelioration of bilirubin glucuronidation defect in Gunn rats by transplanting genetically modified immortalized autologous hepatocytes. Cell Transplant 7:607–616PubMedCrossRef Tada K, Roy-Chowdhury N, Prasad V, Kim BH, Manchikalapudi P, Fox IJ, van Duijvendijk P, Bosma PJ, Roy-Chowdhury J (1998) Long-term amelioration of bilirubin glucuronidation defect in Gunn rats by transplanting genetically modified immortalized autologous hepatocytes. Cell Transplant 7:607–616PubMedCrossRef
97.
go back to reference Branchereau S, Ferry N, Myara A, Sato H, Kowai O, Trivin F, Houssin D, Danos O, Heard J (1993) Correction of bilirubin glucuronyl transferase in Gunn rats by gene transfer in the liver using retroviral vectors. Chirurgie 119:642–648PubMed Branchereau S, Ferry N, Myara A, Sato H, Kowai O, Trivin F, Houssin D, Danos O, Heard J (1993) Correction of bilirubin glucuronyl transferase in Gunn rats by gene transfer in the liver using retroviral vectors. Chirurgie 119:642–648PubMed
98.
go back to reference van der Wegen P, Louwen R, Imam AM, Buijs-Offerman RM, Sinaasappel M, Grosveld F, Scholte BJ (2006) Successful treatment of UGT1A1 deficiency in a rat model of Crigler-Najjar disease by intravenous administration of a liver-specific lentiviral vector. Mol Ther 13:374–381PubMedCrossRef van der Wegen P, Louwen R, Imam AM, Buijs-Offerman RM, Sinaasappel M, Grosveld F, Scholte BJ (2006) Successful treatment of UGT1A1 deficiency in a rat model of Crigler-Najjar disease by intravenous administration of a liver-specific lentiviral vector. Mol Ther 13:374–381PubMedCrossRef
99.
go back to reference Seppen J, Bakker C, de Jong B, Kunne C, van den Oever K, Vandenberghe K, de Waart R, Twisk J, Bosma P (2006) Adeno-associated virus vector serotypes mediate sustained correction of bilirubin UDP glucuronosyltransferase deficiency in rats. Mol Ther 13:1085–1092PubMedCrossRef Seppen J, Bakker C, de Jong B, Kunne C, van den Oever K, Vandenberghe K, de Waart R, Twisk J, Bosma P (2006) Adeno-associated virus vector serotypes mediate sustained correction of bilirubin UDP glucuronosyltransferase deficiency in rats. Mol Ther 13:1085–1092PubMedCrossRef
100.
go back to reference Montenegro-Miranda PS, Paneda A, Ten BL, Duijst S, de Waart DR, Aseguinolaza GG, Bosma PJ (2013) Adeno-associated viral vector serotype 5 poorly transduces liver in rat models. PLoS One 8:e82597PubMedCentralPubMedCrossRef Montenegro-Miranda PS, Paneda A, Ten BL, Duijst S, de Waart DR, Aseguinolaza GG, Bosma PJ (2013) Adeno-associated viral vector serotype 5 poorly transduces liver in rat models. PLoS One 8:e82597PubMedCentralPubMedCrossRef
101.
go back to reference Montenegro-Miranda PS, Pichard V, Aubert D, Ten BL, Duijst S, de Waart DR, Ferry N, Bosma PJ (2014) In the rat liver, adenoviral gene transfer efficiency is comparable to AAV. Gene Ther 21:168–174PubMedCrossRef Montenegro-Miranda PS, Pichard V, Aubert D, Ten BL, Duijst S, de Waart DR, Ferry N, Bosma PJ (2014) In the rat liver, adenoviral gene transfer efficiency is comparable to AAV. Gene Ther 21:168–174PubMedCrossRef
102.
go back to reference Philipp T, Durazzo M, Trautwein C, Alex B, Straub P, Lamb JG, Johnson EF, Tukey RH, Manns MP (1994) Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet 344:578–581PubMedCrossRef Philipp T, Durazzo M, Trautwein C, Alex B, Straub P, Lamb JG, Johnson EF, Tukey RH, Manns MP (1994) Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet 344:578–581PubMedCrossRef
103.
go back to reference Strassburg CP, Obermayer-Straub P, Alex B, Durazzo M, Rizzetto M, Tukey RH, Manns MP (1996) Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Gastroenterology 111:1576–1586PubMedCrossRef Strassburg CP, Obermayer-Straub P, Alex B, Durazzo M, Rizzetto M, Tukey RH, Manns MP (1996) Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Gastroenterology 111:1576–1586PubMedCrossRef
104.
go back to reference Bachrich T, Thalhammer T, Jager W, Haslmayer P, Alihodzic B, Bakos S, Hitchman E, Senderowicz AM, Penner E (2001) Characterization of autoantibodies against uridine-diphosphate glucuronosyltransferase in patients with inflammatory liver diseases. Hepatology 33:1053–1059PubMedCrossRef Bachrich T, Thalhammer T, Jager W, Haslmayer P, Alihodzic B, Bakos S, Hitchman E, Senderowicz AM, Penner E (2001) Characterization of autoantibodies against uridine-diphosphate glucuronosyltransferase in patients with inflammatory liver diseases. Hepatology 33:1053–1059PubMedCrossRef
105.
go back to reference Keitel V, Burdelski M, Vojnisek Z, Schmitt L, Haussinger D, Kubitz R (2009) De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: a novel mechanism of cholestasis. Hepatology 50:510–517PubMedCrossRef Keitel V, Burdelski M, Vojnisek Z, Schmitt L, Haussinger D, Kubitz R (2009) De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: a novel mechanism of cholestasis. Hepatology 50:510–517PubMedCrossRef
106.
go back to reference Astermark J (2006) Basic aspects of inhibitors to factors VIII and IX and the influence of non-genetic risk factors. Haemophilia 12(Suppl 6):8–13PubMedCrossRef Astermark J (2006) Basic aspects of inhibitors to factors VIII and IX and the influence of non-genetic risk factors. Haemophilia 12(Suppl 6):8–13PubMedCrossRef
107.
go back to reference Seppen J, van Til NP, van der Rijt R, Hiralall JK, Kunne C, Elferink RP (2006) Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats. Gene Ther 13:672–677PubMedCrossRef Seppen J, van Til NP, van der Rijt R, Hiralall JK, Kunne C, Elferink RP (2006) Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats. Gene Ther 13:672–677PubMedCrossRef
108.
go back to reference Takahashi M, Ilan Y, Chowdhury NR, Guida J, Horwitz M, Chowdhury JR (1996) Long term correction of bilirubin-UDP-glucuronosyltransferase deficiency in Gunn rats by administration of a recombinant adenovirus during the neonatal period. J Biol Chem 271:26536–26542PubMedCrossRef Takahashi M, Ilan Y, Chowdhury NR, Guida J, Horwitz M, Chowdhury JR (1996) Long term correction of bilirubin-UDP-glucuronosyltransferase deficiency in Gunn rats by administration of a recombinant adenovirus during the neonatal period. J Biol Chem 271:26536–26542PubMedCrossRef
109.
go back to reference Askari FK, Hitomi Y, Mao M, Wilson JM (1996) Complete correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar syndrome type I following transient in vivo adenovirus-mediated expression of human bilirubin UDP-glucuronosyltransferase. Gene Ther 3:381–388PubMed Askari FK, Hitomi Y, Mao M, Wilson JM (1996) Complete correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar syndrome type I following transient in vivo adenovirus-mediated expression of human bilirubin UDP-glucuronosyltransferase. Gene Ther 3:381–388PubMed
110.
go back to reference Gao G, Lebherz C, Weiner DJ, Grant R, Calcedo R, McCullough B, Bagg A, Zhang Y, Wilson JM (2004) Erythropoietin gene therapy leads to autoimmune anemia in macaques. Blood 103:3300–3302PubMedCrossRef Gao G, Lebherz C, Weiner DJ, Grant R, Calcedo R, McCullough B, Bagg A, Zhang Y, Wilson JM (2004) Erythropoietin gene therapy leads to autoimmune anemia in macaques. Blood 103:3300–3302PubMedCrossRef
111.
go back to reference Chenuaud P, Larcher T, Rabinowitz JE, Provost N, Cherel Y, Casadevall N, Samulski RJ, Moullier P (2004) Autoimmune anemia in macaques following erythropoietin gene therapy. Blood 103:3303–3304PubMedCrossRef Chenuaud P, Larcher T, Rabinowitz JE, Provost N, Cherel Y, Casadevall N, Samulski RJ, Moullier P (2004) Autoimmune anemia in macaques following erythropoietin gene therapy. Blood 103:3303–3304PubMedCrossRef
112.
113.
go back to reference Montenegro-Miranda PS, Ten BL, Kunne C, de Waart DR, Bosma PJ (2011) Mycophenolate mofetil impairs transduction of single-stranded adeno-associated viral vectors. Hum Gene Ther 22:605–612PubMedCrossRef Montenegro-Miranda PS, Ten BL, Kunne C, de Waart DR, Bosma PJ (2011) Mycophenolate mofetil impairs transduction of single-stranded adeno-associated viral vectors. Hum Gene Ther 22:605–612PubMedCrossRef
114.
go back to reference Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, Rouhani F, Conlon TJ, Calcedo R, Betts MR, Spencer C, Byrne BJ, Wilson JM, Flotte TR (2009) Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci U S A 106:16363–16368PubMedCentralPubMedCrossRef Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, Rouhani F, Conlon TJ, Calcedo R, Betts MR, Spencer C, Byrne BJ, Wilson JM, Flotte TR (2009) Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci U S A 106:16363–16368PubMedCentralPubMedCrossRef
115.
go back to reference Brantly ML, Spencer LT, Humphries M, Conlon TJ, Spencer CT, Poirier A, Garlington W, Baker D, Song S, Berns KI, Muzyczka N, Snyder RO, Byrne BJ, Flotte TR (2006) Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Hum Gene Ther 17:1177–1186PubMedCrossRef Brantly ML, Spencer LT, Humphries M, Conlon TJ, Spencer CT, Poirier A, Garlington W, Baker D, Song S, Berns KI, Muzyczka N, Snyder RO, Byrne BJ, Flotte TR (2006) Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Hum Gene Ther 17:1177–1186PubMedCrossRef
116.
go back to reference Flotte TR, Trapnell BC, Humphries M, Carey B, Calcedo R, Rouhani F, Campbell-Thompson M, Yachnis AT, Sandhaus RA, McElvaney NG, Mueller C, Messina LM, Wilson JM, Brantly M, Knop DR, Ye GJ, Chulay JD (2011) Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing alpha1-antitrypsin: interim results. Hum Gene Ther 22:1239–1247PubMedCentralPubMedCrossRef Flotte TR, Trapnell BC, Humphries M, Carey B, Calcedo R, Rouhani F, Campbell-Thompson M, Yachnis AT, Sandhaus RA, McElvaney NG, Mueller C, Messina LM, Wilson JM, Brantly M, Knop DR, Ye GJ, Chulay JD (2011) Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing alpha1-antitrypsin: interim results. Hum Gene Ther 22:1239–1247PubMedCentralPubMedCrossRef
117.
go back to reference Worgall S, Sondhi D, Hackett NR, Kosofsky B, Kekatpure MV, Neyzi N, Dyke JP, Ballon D, Heier L, Greenwald BM, Christos P, Mazumdar M, Souweidane MM, Kaplitt MG, Crystal RG (2008) Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther 19:463–474PubMedCrossRef Worgall S, Sondhi D, Hackett NR, Kosofsky B, Kekatpure MV, Neyzi N, Dyke JP, Ballon D, Heier L, Greenwald BM, Christos P, Mazumdar M, Souweidane MM, Kaplitt MG, Crystal RG (2008) Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther 19:463–474PubMedCrossRef
118.
go back to reference Wagner JA, Reynolds T, Moran ML, Moss RB, Wine JJ, Flotte TR, Gardner P (1998) Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus. Lancet 351:1702–1703PubMedCrossRef Wagner JA, Reynolds T, Moran ML, Moss RB, Wine JJ, Flotte TR, Gardner P (1998) Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus. Lancet 351:1702–1703PubMedCrossRef
119.
go back to reference Wagner JA, Messner AH, Moran ML, Daifuku R, Kouyama K, Desch JK, Manley S, Norbash AM, Conrad CK, Friborg S, Reynolds T, Guggino WB, Moss RB, Carter BJ, Wine JJ, Flotte TR, Gardner P (1999) Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Laryngoscope 109:266–274PubMedCrossRef Wagner JA, Messner AH, Moran ML, Daifuku R, Kouyama K, Desch JK, Manley S, Norbash AM, Conrad CK, Friborg S, Reynolds T, Guggino WB, Moss RB, Carter BJ, Wine JJ, Flotte TR, Gardner P (1999) Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus. Laryngoscope 109:266–274PubMedCrossRef
120.
go back to reference Wagner JA, Nepomuceno IB, Messner AH, Moran ML, Batson EP, Dimiceli S, Brown BW, Desch JK, Norbash AM, Conrad CK, Guggino WB, Flotte TR, Wine JJ, Carter BJ, Reynolds TC, Moss RB, Gardner P (2002) A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Hum Gene Ther 13:1349–1359PubMedCrossRef Wagner JA, Nepomuceno IB, Messner AH, Moran ML, Batson EP, Dimiceli S, Brown BW, Desch JK, Norbash AM, Conrad CK, Guggino WB, Flotte TR, Wine JJ, Carter BJ, Reynolds TC, Moss RB, Gardner P (2002) A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Hum Gene Ther 13:1349–1359PubMedCrossRef
121.
go back to reference Moss RB, Rodman D, Spencer LT, Aitken ML, Zeitlin PL, Waltz D, Milla C, Brody AS, Clancy JP, Ramsey B, Hamblett N, Heald AE (2004) Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 125:509–521PubMedCrossRef Moss RB, Rodman D, Spencer LT, Aitken ML, Zeitlin PL, Waltz D, Milla C, Brody AS, Clancy JP, Ramsey B, Hamblett N, Heald AE (2004) Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 125:509–521PubMedCrossRef
122.
go back to reference Aitken ML, Moss RB, Waltz DA, Dovey ME, Tonelli MR, McNamara SC, Gibson RL, Ramsey BW, Carter BJ, Reynolds TC (2001) A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease. Hum Gene Ther 12:1907–1916PubMedCrossRef Aitken ML, Moss RB, Waltz DA, Dovey ME, Tonelli MR, McNamara SC, Gibson RL, Ramsey BW, Carter BJ, Reynolds TC (2001) A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease. Hum Gene Ther 12:1907–1916PubMedCrossRef
123.
go back to reference Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Rustagi PK, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006) Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med 12:342–347PubMedCrossRef Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Rustagi PK, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006) Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med 12:342–347PubMedCrossRef
124.
go back to reference Manno CS, Chew AJ, Hutchison S, Larson PJ, Herzog RW, Arruda VR, Tai SJ, Ragni MV, Thompson A, Ozelo M, Couto LB, Leonard DG, Johnson FA, McClelland A, Scallan C, Skarsgard E, Flake AW, Kay MA, High KA, Glader B (2003) AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 101:2963–2972PubMedCrossRef Manno CS, Chew AJ, Hutchison S, Larson PJ, Herzog RW, Arruda VR, Tai SJ, Ragni MV, Thompson A, Ozelo M, Couto LB, Leonard DG, Johnson FA, McClelland A, Scallan C, Skarsgard E, Flake AW, Kay MA, High KA, Glader B (2003) AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 101:2963–2972PubMedCrossRef
125.
go back to reference Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358:2240–2248PubMedCentralPubMedCrossRef Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358:2240–2248PubMedCentralPubMedCrossRef
126.
go back to reference Testa F, Maguire AM, Rossi S, Pierce EA, Melillo P, Marshall K, Banfi S, Surace EM, Sun J, Acerra C, Wright JF, Wellman J, High KA, Auricchio A, Bennett J, Simonelli F (2013) Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital amaurosis type 2. Ophthalmology 120:1283–1291PubMedCentralPubMedCrossRef Testa F, Maguire AM, Rossi S, Pierce EA, Melillo P, Marshall K, Banfi S, Surace EM, Sun J, Acerra C, Wright JF, Wellman J, High KA, Auricchio A, Bennett J, Simonelli F (2013) Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital amaurosis type 2. Ophthalmology 120:1283–1291PubMedCentralPubMedCrossRef
127.
go back to reference Ashtari M, Cyckowski LL, Monroe JF, Marshall KA, Chung DC, Auricchio A, Simonelli F, Leroy BP, Maguire AM, Shindler KS, Bennett J (2011) The human visual cortex responds to gene therapy-mediated recovery of retinal function. J Clin Invest 121:2160–2168PubMedCentralPubMedCrossRef Ashtari M, Cyckowski LL, Monroe JF, Marshall KA, Chung DC, Auricchio A, Simonelli F, Leroy BP, Maguire AM, Shindler KS, Bennett J (2011) The human visual cortex responds to gene therapy-mediated recovery of retinal function. J Clin Invest 121:2160–2168PubMedCentralPubMedCrossRef
128.
go back to reference Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A (2010) Gene therapy for Leber’s congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther 18:643–650PubMedCentralPubMedCrossRef Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A (2010) Gene therapy for Leber’s congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther 18:643–650PubMedCentralPubMedCrossRef
129.
go back to reference Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358:2231–2239PubMedCrossRef Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358:2231–2239PubMedCrossRef
130.
go back to reference Gaudet D, Methot J, Dery S, Brisson D, Essiembre C, Tremblay G, Tremblay K, de Wal J, Twisk J, van den Bulk N, Sier-Ferreira V, van Deventer S (2013) Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther 20:361–369PubMedCrossRef Gaudet D, Methot J, Dery S, Brisson D, Essiembre C, Tremblay G, Tremblay K, de Wal J, Twisk J, van den Bulk N, Sier-Ferreira V, van Deventer S (2013) Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther 20:361–369PubMedCrossRef
131.
go back to reference Stroes ES, Nierman MC, Meulenberg JJ, Franssen R, Twisk J, Henny CP, Maas MM, Zwinderman AH, Ross C, Aronica E, High KA, Levi MM, Hayden MR, Kastelein JJ, Kuivenhoven JA (2008) Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol 28:2303–2304PubMedCrossRef Stroes ES, Nierman MC, Meulenberg JJ, Franssen R, Twisk J, Henny CP, Maas MM, Zwinderman AH, Ross C, Aronica E, High KA, Levi MM, Hayden MR, Kastelein JJ, Kuivenhoven JA (2008) Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol 28:2303–2304PubMedCrossRef
132.
go back to reference Smith BK, Collins SW, Conlon TJ, Mah CS, Lawson LA, Martin AD, Fuller DD, Cleaver BD, Clement N, Phillips D, Islam S, Dobjia N, Byrne BJ (2013) Phase I/II trial of adeno-associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respiratory failure in Pompe disease: initial safety and ventilatory outcomes. Hum Gene Ther 24:630–640PubMedCentralPubMedCrossRef Smith BK, Collins SW, Conlon TJ, Mah CS, Lawson LA, Martin AD, Fuller DD, Cleaver BD, Clement N, Phillips D, Islam S, Dobjia N, Byrne BJ (2013) Phase I/II trial of adeno-associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respiratory failure in Pompe disease: initial safety and ventilatory outcomes. Hum Gene Ther 24:630–640PubMedCentralPubMedCrossRef
133.
go back to reference Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X, Samulski J, McPhee SW, Samulski RJ, Walker CM (2010) Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med 363:1429–1437PubMedCentralPubMedCrossRef Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X, Samulski J, McPhee SW, Samulski RJ, Walker CM (2010) Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med 363:1429–1437PubMedCentralPubMedCrossRef
134.
go back to reference Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, Li J, Wang B, Monahan PE, Rabinowitz JE, Grieger JC, Govindasamy L, Agbandje-McKenna M, Xiao X, Samulski RJ (2012) Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther 20:443–455PubMedCentralPubMedCrossRef Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, Li J, Wang B, Monahan PE, Rabinowitz JE, Grieger JC, Govindasamy L, Agbandje-McKenna M, Xiao X, Samulski RJ (2012) Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther 20:443–455PubMedCentralPubMedCrossRef
135.
go back to reference Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR (2010) Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol 68:629–638PubMedCentralPubMedCrossRef Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR (2010) Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol 68:629–638PubMedCentralPubMedCrossRef
136.
go back to reference Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR (2009) Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol 66:290–297PubMedCrossRef Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR (2009) Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol 66:290–297PubMedCrossRef
137.
go back to reference Mendell JR, Rodino-Klapac L, Sahenk Z, Malik V, Kaspar BK, Walker CM, Clark KR (2012) Gene therapy for muscular dystrophy: lessons learned and path forward. Neurosci Lett 527:90–99PubMedCentralPubMedCrossRef Mendell JR, Rodino-Klapac L, Sahenk Z, Malik V, Kaspar BK, Walker CM, Clark KR (2012) Gene therapy for muscular dystrophy: lessons learned and path forward. Neurosci Lett 527:90–99PubMedCentralPubMedCrossRef
Metadata
Title
Gene Replacement Therapy for Genetic Hepatocellular Jaundice
Authors
Remco van Dijk
Ulrich Beuers
Piter J. Bosma
Publication date
01-06-2015
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 2-3/2015
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-014-8454-7

Other articles of this Issue 2-3/2015

Clinical Reviews in Allergy & Immunology 2-3/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine