Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model

EMBO Molecular Medicine

Volumn 9, Issue 10, 2017, Pages 1346-1355

  Porro, Fabiola ^a   Bortolussi, Giulia ^a   Barzel, Adi ^b,c   De Caneva, Alessia ^a   Iaconcig, Alessandra ^a   Vodret, Simone ^a   Zentilin, Lorena ^a   Kay, Mark A ^b   Muro, Andrés F ^a  

^a INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY   (Italy)

^b STANFORD UNIVERSITY   (United States)

^c TEL AVIV UNIVERSITY   (Israel)

Author keywords

brain damage; genetic liver disease; homologous recombination; hyperbilirubinemia; kernicterus

Indexed keywords

ALBUMIN; BILIRUBIN; COMPLEMENTARY DNA; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE; UGT1A1 ENZYME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; BILIRUBIN BLOOD LEVEL; CLINICAL EFFECTIVENESS; CONFERENCE PAPER; CONTROLLED STUDY; CRIGLER NAJJAR SYNDROME TYPE I; FEASIBILITY STUDY; GENE LOCUS; GENE TARGETING; GENE THERAPY; HISTOLOGY; IN VIVO STUDY; LETHALITY; MOTOR COORDINATION; MOUSE; NEWBORN; NONHUMAN; PHOTOTHERAPY; PRIORITY JOURNAL; PROMOTERLESS GENE THERAPY; PROTEIN EXPRESSION; SURVIVAL; UGT1A1 GENE; ANIMAL; BLOOD; BRAIN; CRIGLER NAJJAR SYNDROME; DISEASE MODEL; GENETIC TRANSDUCTION; GENETICS; HUMAN; HYPERBILIRUBINEMIA; LIVER; METABOLISM; MUTANT MOUSE STRAIN; PATHOLOGY; PROCEDURES; PROMOTER REGION; SURVIVAL ANALYSIS;

ANIMALS; BILIRUBIN; BRAIN; CRIGLER-NAJJAR SYNDROME; DISEASE MODELS, ANIMAL; GENE TARGETING; GENETIC THERAPY; GLUCURONOSYLTRANSFERASE; HUMANS; HYPERBILIRUBINEMIA; LIVER; MICE; MICE, MUTANT STRAINS; PROMOTER REGIONS, GENETIC; SURVIVAL ANALYSIS; TRANSDUCTION, GENETIC;

EID: 85026366009     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.15252/emmm.201707601     Document Type: Conference Paper

References (49)

1. Adam R, Karam V, Delvart V, O'Grady J, Mirza D, Klempnauer J, Castaing D, Neuhaus P, Jamieson N, Salizzoni M et al (2012) Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol 57: 675–688
2. Anguela XM, Sharma R, Doyon Y, Miller JC, Li H, Haurigot V, Rohde ME, Wong SY, Davidson RJ, Zhou S et al (2013) Robust ZFN-mediated genome editing in adult hemophilic mice. Blood 122: 3283–3287
3. 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: 298–301
4. Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector LP, Porteus MH, Gaensler KM et al (2015) Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517: 360–364
5. 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-human primates. Mol Genet Metab 104: 395–403
6. 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-/- lethal mouse model of neonatal hyperbilirubinemia. Hum Mol Genet 26: 145–157
7. Bortolussi G, Zentilin L, Baj G, Giraudi P, Bellarosa C, Giacca M, Tiribelli C, Muro AF (2012) Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. FASEB J 26: 1052–1063
8. Bortolussi G, Baj G, Vodret S, Viviani G, Bittolo T, Muro AF (2014a) Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo. Dis Model Mech 7: 1057–1068
9. Bortolussi G, Zentilin L, Vanikova J, Bockor L, Bellarosa C, Mancarella A, Vianello E, Tiribelli C, Giacca M, Vitek L et al (2014b) 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 25: 844–855
10. Bosma PJ (2003) Inherited disorders of bilirubin metabolism. J Hepatol 38: 107–117
11. 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: 273–280
12. Carroll D (2014) Genome engineering with targetable nucleases. Annu Rev Biochem 83: 409–439
13. Chandler RJ, LaFave MC, Varshney GK, Trivedi NS, Carrillo-Carrasco N, Senac JS, Wu W, Hoffmann V, Elkahloun AG, Burgess SM et al (2015) Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J Clin Investig 125: 870–880
14. Crigler JF Jr, Najjar VA (1952) Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10: 169–180
15. 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: 1081–1088
16. Dane AP, Wowro SJ, Cunningham SC, Alexander IE (2013) Comparison of gene transfer to the murine liver following intraperitoneal and intraportal delivery of hepatotropic AAV pseudo-serotypes. Gene Ther 20: 460–464
17. 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
18. Emi Y, Omura S, Ikushiro S, Iyanagi T (2002) Accelerated degradation of mislocalized UDP-glucuronosyltransferase family 1 (UGT1) proteins in Gunn rat hepatocytes. Arch Biochem Biophys 405: 163–169
19. Fagiuoli S, Daina E, D'Antiga L, Colledan M, Remuzzi G (2013) Monogenic diseases that can be cured by liver transplantation. J Hepatol 59: 595–612
20. 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: 1422–1426
21. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013) High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31: 822–826
22. Huang PW, Rozdilsky B, Gerrard JW, Goluboff N, Holman GH (1970) Crigler-Najjar syndrome in four of five siblings with postmortem findings in one. Arch Pathol 90: 536–539
23. 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: 2290–2292
24. Joung JK, Sander JD (2013) TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14: 49–55
25. Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR (2000) Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 16: 297–306
26. Kay MA (2011) State-of-the-art gene-based therapies: the road ahead. Nat Rev Genet 12: 316–328
27. Maruyama T, Dougan SK, Truttmann MC, Bilate AM, Ingram JR, Ploegh HL (2015) Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol 33: 538–542
28. Mingozzi F, High KA (2011) Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 12: 341–355
29. Murphy SL, Li H, Mingozzi F, Sabatino DE, Hui DJ, Edmonson SA, High KA (2009) Diverse IgG subclass responses to adeno-associated virus infection and vector administration. J Med Virol 81: 65–74
30. Nathwani AC, Cochrane M, McIntosh J, Ng CY, Zhou J, Gray JT, Davidoff AM (2009) Enhancing transduction of the liver by adeno-associated viral vectors. Gene Ther 16: 60–69
31. Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C et al (2011) Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 365: 2357–2365
32. Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D et al (2014) Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 371: 1994–2004
33. Nygaard S, Barzel A, Haft A, Major A, Finegold M, Kay MA, Grompe M (2016) A universal system to select gene-modified hepatocytes in vivo. Sci Transl Med 8: 342ra379
34. Paulk NK, Loza LM, Finegold MJ, Grompe M (2012) AAV-mediated gene targeting is significantly enhanced by transient inhibition of nonhomologous end joining or the proteasome in vivo. Hum Gene Ther 23: 658–665
35. Pinkert CA, Ornitz DM, Brinster RL, Palmiter RD (1987) An albumin enhancer located 10 kb upstream functions along with its promoter to direct efficient, liver-specific expression in transgenic mice. Genes Dev 1: 268–276
36. Poliard AM, Bernuau D, Tournier I, Legres LG, Schoevaert D, Feldmann G, Sala-Trepat JM (1986) Cellular analysis by in situ hybridization and immunoperoxidase of alpha-fetoprotein and albumin gene expression in rat liver during the perinatal period. J Cell Biol 103: 777–786
37. Riviere C, Danos O, Douar AM (2006) Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice. Gene Ther 13: 1300–1308
38. Ronzitti G, Bortolussi G, van Dijk R, Collaud F, Charles S, Leborgne C, Vidal P, Martin S, Gjata B, Sola MS et al (2016) A translationally optimized AAV-UGT1A1 vector drives safe and long-lasting correction of Crigler-Najjar syndrome. Mol Ther Methods Clin Dev 3: 16049
39. Russell DW, Hirata RK (1998) Human gene targeting by viral vectors. Nat Genet 18: 325–330
40. Sharma R, Anguela XM, Doyon Y, Wechsler T, DeKelver RC, Sproul S, Paschon DE, Miller JC, Davidson RJ, Shivak D et al (2015) In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood 126: 1777–1784
41. Sneitz N, Bakker CT, de Knegt RJ, Halley DJ, Finel M, Bosma PJ (2010) Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants. Hum Mutat 31: 52–59
42. Srivastava M, Nambiar M, Sharma S, Karki SS, Goldsmith G, Hegde M, Kumar S, Pandey M, Singh RK, Ray P et al (2012) An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell 151: 1474–1487
43. Tilghman SM, Belayew A (1982) Transcriptional control of the murine albumin/alpha-fetoprotein locus during development. Proc Natl Acad Sci USA 79: 5254–5257
44. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11: 636–646
45. Valdmanis PN, Lisowski L, Kay MA (2012) rAAV-mediated tumorigenesis: still unresolved after an AAV assault. Mol Ther 20: 2014–2017
46. −/− mouse model. J Neuroinflammation 14: 64
47. Wang L, Wang H, Bell P, McMenamin D, Wilson JM (2012) Hepatic gene transfer in neonatal mice by adeno-associated virus serotype 8 vector. Hum Gene Ther 23: 533–539
48. Wang H, La Russa M, Qi LS (2016) CRISPR/Cas9 in genome editing and beyond. Annu Rev Biochem 85: 227–264
49. Yang Y, Wang L, Bell P, McMenamin D, He Z, White J, Yu H, Xu C, Morizono H, Musunuru K et al (2016) A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol 34: 334–338