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Progress and challenges in gene therapy for Crigler–Najjar syndrome

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Bibliography

References of special note have been highlighted as either of interest (*) or of considerable interest (**) to readers.

  • Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357–2365. First successful in man AAV mediated liver-directed gene therapy trial for the treatment of hemophilia B.
  • Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013;341(6148):1233151.
  • Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature. 2010;467(7313):318–322.
  • Hacein-Bey-Abina S, Pai SY, Gaspar HB, et al. A modified gamma-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med. 2014;371(15):1407–1417.
  • Stroes ES, Nierman MC, Meulenberg JJ, et al. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol. 2008;28(12):2303–2304. This paper led to the first registered gene therapy product in Europe.
  • Gaudet D, Methot J, Dery S, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther. 2013;20(4):361–369.
  • Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004. Report of 4-year follow-up of the first AAV mediated liver-directed gene therapy trial for the treatment of hemophilia B. Provides proof of principle of the efficacy of liver-directed gene therapy in man.
  • Bosma PJ, Seppen J, Goldhoorn B, et al. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem. 1994;269(27):17960–17964.
  • Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). J Perinatol. 2005;25(1):54–59.
  • Monaghan G, Ryan M, Seddon R, et al. Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 1996;347(9001):578–581.
  • Owens D, Evans J. Population studies on Gilbert’s syndrome. J Med Genet. 1975;12(2):152–156.
  • Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333(18):1171–1175.
  • Black M, Billing BH. Hepatic bilirubin UDP-glucuronyl transferase activity in liver disease and Gilbert’s syndrome. N Engl J Med. 1969;280(23):1266–1271.
  • Maruo Y, Nishizawa K, Sato H, et al. Association of neonatal hyperbilirubinemia with bilirubin UDP-glucuronosyltransferase polymorphism. Pediatrics. 1999;103 (6 Pt 1):1224–1227.
  • Crigler JF Jr., Najjar VA. Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics. 1952;10(2):169–180.
  • Canu G, Minucci A, Zuppi C, et al. Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood Cells Mol Dis. 2013;50(4):273–280.
  • Sneitz N, Bakker CT, de Knegt RJ, et al. Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants. Hum Mutat. 2010;31(1):52–59.
  • Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage–mechanisms and management approaches. N Engl J Med. 2013;369(21):2021–2030.
  • Poddar B, Bharti B, Goraya J, et al. Kernicterus in a child with Crigler-Najjar syndrome type II. Trop Gastroenterol. 2002;23(1):33–34.
  • Arias IM, Gartner LM, Cohen M, et al. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med. 1969;47(3):395–409.
  • Sugatani J. Function, genetic polymorphism, and transcriptional regulation of human UDP-glucuronosyltransferase (UGT) 1A1. Drug Metab Pharmacokinet. 2013;28(2):83–92.
  • Enoru-Eta J, Yengi LG, He X, et al. Development of a UGT1A1 reporter gene assay for induction studies: correlation between reporter gene data and regulation of UGT1A1 in human hepatocytes. Drug Metab Lett. 2010;4(1):31–38.
  • Sugatani J, Sueyoshi T, Negishi M, et al. Regulation of the human UGT1A1 gene by nuclear receptors constitutive active/androstane receptor, pregnane X receptor, and glucocorticoid receptor. Methods Enzymol. 2005;400:92–104.
  • van Dijk R, Kremer AE, Smit W, et al. Characterization and treatment of persistent hepatocellular secretory failure. Liver Int. 2014 35(4):1478–1488.
  • Strauss KA, Robinson DL, Vreman HJ, et al. Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease. Eur J Pediatr. 2006;165(5):306–319.
  • Van Der Veere CN, Sinaasappel M, McDonagh AF, et al. Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology. 1996;24(2):311–315.
  • Yohannan MD, Terry HJ, Littlewood JM. Long term phototherapy in Crigler-Najjar syndrome. Arch Dis Child. 1983;58(6):460–462.
  • Fagiuoli S, Daina E, D’Antiga L, et al. Monogenic diseases that can be cured by liver transplantation. J Hepatol. 2013;59(3):595–612.
  • Adam R, Karam V, Delvart V, et al. Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol. 2012;57(3):675–688.
  • Fox IJ, Chowdhury JR, Kaufman SS, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. 1998;338(20):1422–1426.
  • Ambrosino G, Varotto S, Strom SC, et al. Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant. 2005;14 (2–3):151–157.
  • Lysy PA, Najimi M, Stephenne X, et al. Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives. World J Gastroenterol. 2008;14(22):3464–3470.
  • Huch M, Gehart H, van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2015;160 (1–2):299–312.
  • Giacca M, Zacchigna S. Virus-mediated gene delivery for human gene therapy. J Control Release. 2012;161(2):377–388.
  • Kay MA. State-of-the-art gene-based therapies: the road ahead. Nat Rev Genet. 2011;12(5):316–328.
  • Vannucci L, Lai M, Chiuppesi F, et al. Viral vectors: a look back and ahead on gene transfer technology. New Microbiol. 2013;36(1):1–22.
  • Wang D, Gao G. State-of-the-art human gene therapy: part I. Gene delivery technologies. Discov Med. 2014;18(97):67–77.
  • Cavazza A, Moiani A, Mavilio F. Mechanisms of retroviral integration and mutagenesis. Hum Gene Ther. 2013;24(2):119–131.
  • Naldini L. Ex vivo gene transfer and correction for cell-based therapies. Nat Rev Genet. 2011;12(5):301–315.
  • Touzot F, Hacein-Bey-Abina S, Fischer A, et al. Gene therapy for inherited immunodeficiency. Expert Opin Biol Ther. 2014;14(6):789–798.
  • Raper SE, Chirmule N, Lee FS, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003;80 (1–2):148–158.
  • Mingozzi F, High KA. Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Reviews Genet. 2011;12(5):341–355.
  • Miller DG, Petek LM, Russell DW. Adeno-associated virus vectors integrate at chromosome breakage sites. Nat Genet. 2004;36(7):767–773.
  • Donsante A, Miller DG, Li Y, et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science. 2007;317(5837):477.
  • Bell P, Wang L, Lebherz C, et al. No evidence for tumorigenesis of AAV vectors in a large-scale study in mice. Mol Ther. 2005;12(2):299–306.
  • Li H, Malani N, Hamilton SR, et al. Assessing the potential for AAV vector genotoxicity in a murine model. Blood. 2011;117(12):3311–3319.
  • Niemeyer GP, Herzog RW, Mount J, et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood. 2009;113(4):797–806.
  • Nathwani AC, Rosales C, McIntosh J, et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther. 2011;19(5):876–885.
  • Chandler RJ, LaFave MC, Varshney GK, et al. Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J Clin Invest. 2015;125(2):870–880.
  • Junge N, Mingozzi F, Ott M, et al. Adeno-associated virus vector based gene therapy for monogenetic metabolic diseases of the liver. J Pediatr Gastroenterol Nutr. 2015;60(4):433–440. Comprehensive review on different AAV gene transfer strategies for metabolic diseases of the liver in general.
  • Gunn CH. Hereditary acholuric jaundice in a new mutant strain of rats. J Hered. 1938;29:137–139.
  • Miranda PS, Bosma PJ. Towards liver-directed gene therapy for Crigler-Najjar syndrome. Curr Gene Ther. 2009;9(2):72–82. Comprehensive review on different viral gene transfer strategies for Crigler–Najjar syndrome.
  • Branchereau S, Ferry N, Myara A, et al. Correction of bilirubin glucuronyl transferase in Gunn rats by gene transfer in the liver using retroviral vectors. Chirurgie. 1993;119(10):642–648.
  • Roy-Chowdhury N, Kadakol A, Sappal BS, et al. Gene therapy for inherited hyperbilirubinemias. J Perinatol. 2001;21 (Suppl 1):S114–S118; discussion S25–S27.
  • van der Wegen P, Louwen R, Imam AM, et al. Successful treatment of UGT1A1 deficiency in a rat model of Crigler-Najjar disease by intravenous administration of a liver-specific lentiviral vector. Mol Ther. 2006;13(2):374–381.
  • Seppen J, Tada K, Ottenhoff R, et al. Transplantation of Gunn rats with autologous fibroblasts expressing bilirubin UDP-glucuronosyltransferase: correction of genetic deficiency and tumor formation. Hum Gene Ther. 1997;8(1):27–36. This paper demonstrates that expression of UGT1A1 in other tissues effectively corrected Crigler-Najjar syndrome.
  • Bortolussi G, Zentillin L, Vanikova J, et al. Life-long correction of hyperbilirubinemia with a neonatal liver-specific AAV-mediated gene transfer in a lethal mouse model of Crigler-Najjar syndrome. Hum Gene Ther. 2014;25(9):844–855. This paper nicely demonstrates efficacy of AAV-mediated gene therapy for Crigler-Najjar in a mouse model.
  • Schmitt F, Remy S, Dariel A, et al. Lentiviral vectors that express UGT1A1 in liver and contain miR-142 target sequences normalize hyperbilirubinemia in Gunn rats. Gastroenterology. 2010;139(3):999–1007, 07.e1–2.
  • Schmitt F, Pastore N, Abarrategui-Pontes C, et al. Correction of hyperbilirubinemia in Gunn rats by surgical delivery of low doses of helper-dependent adenoviral vectors. Hum Gene Ther Methods. 2014;25(3):181–186.
  • Seppen J, Bakker C, de Jong B, et al. Adeno-associated virus vector serotypes mediate sustained correction of bilirubin UDP glucuronosyltransferase deficiency in rats. Mol Ther. 2006;13(6):1085–1092.
  • Montenegro-Miranda PS, Pichard V, Aubert D, et al. In the rat liver, adenoviral gene transfer efficiency is comparable to AAV. Gene Ther. 2014;21(2):168–174.
  • Bortolussi G, Zentilin L, Baj G, et al. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. Faseb J. 2012;26(3):1052–1063.
  • Hosel M, Broxtermann M, Janicki H, et al. Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors. Hepatology. 2012;55(1):287–297.
  • Zhu J, Huang X, Yang Y. The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice. J Clin Invest. 2009;119(8):2388–2398.
  • Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342–347.
  • Vandenberghe LH, Wang L, Somanathan S, et al. Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid. Nat Med. 2006;12(8):967–971.
  • Montenegro-Miranda PS, ten Bloemendaal L, Kunne C, et al. Mycophenolate mofetil impairs transduction of single-stranded adeno-associated viral vectors. Hum Gene Ther. 2011;22(5):605–612.
  • Mingozzi F, High KA. Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood. 2013;122(1):23–36. This paper summarizes the major challenge of immunogenicity of AAV-mediated gene therapy that still has to be overcome.
  • Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther. 2010;21(6):704–712.
  • Calcedo R, Vandenberghe LH, Gao G, et al. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis. 2009;199(3):381–390.
  • Jiang H, Couto LB, Patarroyo-White S, et al. Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood. 2006;108(10):3321–3328.
  • Murphy SL, Li H, Zhou S, et al. Prolonged susceptibility to antibody-mediated neutralization for adeno-associated vectors targeted to the liver. Mol Ther. 2008;16(1):138–145.
  • Scallan CD, Jiang H, Liu T, et al. Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood. 2006;107(5):1810–1817.
  • Masat E, Pavani G, Mingozzi F. Humoral immunity to AAV vectors in gene therapy: challenges and potential solutions. Discov Med. 2013;15(85):379–389.
  • Tse LV, Moller-Tank S, Asokan A. Strategies to circumvent humoral immunity to adeno-associated viral vectors. Expert Opin Biol Ther. 2015;15(6):845–855.
  • Mingozzi F, Anguela XM, Pavani G, et al. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med. 2013;5(194):194ra92.
  • Mingozzi F, Chen Y, Edmonson SC, et al. Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue. Gene Ther. 2013;20(4):417–424.
  • Monteilhet V, Saheb S, Boutin S, et al. A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8. Mol Ther. 2011;19(11):2084–2091.
  • Nakai H, Yant SR, Storm TA, et al. Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo. J Virol. 2001;75(15):6969–6976.
  • Flageul M, Aubert D, Pichard V, et al. Transient expression of genes delivered to newborn rat liver using recombinant adeno-associated virus 2/8 vectors. J Gene Med. 2009;11(8):689–696.
  • Davidoff AM, Gray JT, Ng CY, et al. Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models. Mol Ther. 2005;11(6):875–888.
  • Lombardo A, Cesana D, Genovese P, et al. Site-specific integration and tailoring of cassette design for sustainable gene transfer. Nat Methods. 2011;8(10):861–869.
  • Sadelain M, Papapetrou EP, Bushman FD. Safe harbours for the integration of new DNA in the human genome. Nat Rev Cancer. 2012;12(1):51–58.
  • Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003;302(5644):415–419.
  • Kim H, Kim JS. A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014;15(5):321–334.
  • Gaj T, Gersbach CA, Barbas CF 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397–405.
  • Li HL, Nakano T, Hotta A. Genetic correction using engineered nucleases for gene therapy applications. Dev Growth Differ. 2014;56(1):63–77.
  • Shrivastav M, De Haro LP, Nickoloff JA. Regulation of DNA double-strand break repair pathway choice. Cell Res. 2008;18(1):134–147.
  • Li H, Haurigot V, Doyon Y, et al. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature. 2011;475(7355):217–221.
  • Barzel A, Paulk NK, Shi Y, et al. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature. 2015;517(7534):360–364. This paper proves efficacy of a promotorless gene targeting strategy in mice and is an example of pioneering work that could have major implications for the field of gene therapy.
  • VandenDriessche T, Chuah MK. Hitting the target without pulling the trigger. Mol Ther. 2015;23(1):4–6.
  • Zhang W, Solanki M, Muther N, et al. Hybrid adeno-associated viral vectors utilizing transposase-mediated somatic integration for stable transgene expression in human cells. PLoS One. 2013;8(10):e76771.
  • Paulk NK, Wursthorn K, Haft A, et al. In vivo selection of transplanted hepatocytes by pharmacological inhibition of fumarylacetoacetate hydrolase in wild-type mice. Mol Ther. 2012;20(10):1981–1987.
  • Viswanathan P, Kapoor S, Kumaran V, et al. Etanercept blocks inflammatory responses orchestrated by TNF-alpha to promote transplanted cell engraftment and proliferation in rat liver. Hepatology. 2014;60(4):1378–1388. This paper reveals the importance of inflammation in the low grafting efficacy of hepatocytes offering novel targets to overcome this hurdle.
  • Wangensteen KJ, Zhang S, Greenbaum LE, et al. A genetic screen reveals Foxa3 and TNFR1 as key regulators of liver repopulation. Genes Dev. 2015;29(9):904–909.

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