Gene Therapy Approaches to Hemoglobinopathies

Hematology/Oncology Clinics of North America

Volumn 31, Issue 5, 2017, Pages 835-852

  Ferrari, Giuliana ^a,b   Cavazzana, Marina ^c,d   Mavilio, Fulvio ^e  

^a SAN RAFFAELE SCIENTIFIC INSTITUTE   (Italy)

^b VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^c HÔPITAL NECKER ENFANTS MALADES   (France)

^d UNIVERSITÉ PARIS DESCARTES   (France)

^e UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

Gene transfer; Globin gene regulation; Hematopoiesis; Lentiviral vectors; Retroviral vectors; Sickle cell disease; Stem cell transplantation; Thalassemia

Indexed keywords

BUSULFAN; GRANULOCYTE COLONY STIMULATING FACTOR; MELPHALAN; PLERIXAFOR; THIOTEPA; TREOSULFAN; HEMOGLOBIN;

ADRENOLEUKODYSTROPHY; BETA GLOBIN GENE; BETA THALASSEMIA; CHRONIC GRANULOMATOUS DISEASE; DRUG EFFICACY; GAMMA GLOBIN GENE; GENE; GENE THERAPY; GENE TRANSFER; HBB GENE; HEMOGLOBINOPATHY; HUMAN; METACHROMATIC LEUKODYSTROPHY; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SEVERE COMBINED IMMUNODEFICIENCY; SICKLE CELL ANEMIA; WISKOTT ALDRICH SYNDROME; X LINKED SEVERE COMBINED IMMUNODEFICIENCY; ADVERSE EFFECTS; ANEMIA, SICKLE CELL; ANIMAL; BETA-THALASSEMIA; CLINICAL TRIAL (TOPIC); CYTOLOGY; GENE EXPRESSION; GENE VECTOR; GENETIC TRANSDUCTION; GENETICS; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMOGLOBINOPATHIES; METABOLISM; PRECLINICAL STUDY; PROCEDURES;

ANEMIA, SICKLE CELL; ANIMALS; BETA-THALASSEMIA; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; GENE EXPRESSION; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMATOPOIETIC STEM CELLS; HEMOGLOBINOPATHIES; HEMOGLOBINS; HUMANS; TRANSDUCTION, GENETIC;

EID: 85029321215     PISSN: 08898588     EISSN: 15581977     Source Type: Journal    
DOI: 10.1016/j.hoc.2017.06.010     Document Type: Review

References (95)

1. Stamatoyannopoulos, G., (eds.) The molecular basis of blood diseases, 3rd edition, 2001, W.B. Saunders Co, Philadelphia.
2. Modell, B., Global epidemiology of hemoglobin disorders and derived service indicators. 2008, World Health Organization, London, 417–496.
3. Locatelli, F., Kabbara, N., Ruggeri, A., et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood 122:6 (2013), 1072–1078.
4. Booth, C., Gaspar, H.B., Thrasher, A.J., Treating Immunodeficiency through HSC gene therapy. Trends Mol Med 22:4 (2016), 317–327.
5. Cavazza, A., Moiani, A., Mavilio, F., Mechanisms of retroviral integration and mutagenesis. Hum Gene Ther 24:2 (2013), 119–131.
6. Biasco, L., Baricordi, C., Aiuti, A., Retroviral integrations in gene therapy trials. Mol Ther 20:4 (2012), 709–716.
7. Hacein-Bey-Abina, S., Pai, S.Y., Gaspar, H.B., et al. A modified gamma-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med 371:15 (2014), 1407–1417.
8. Cattoglio, C., Pellin, D., Rizzi, E., et al. High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors. Blood 116:25 (2010), 5507–5517.
9. De Ravin, S.S., Su, L., Theobald, N., et al. Enhancers are major targets for murine leukemia virus vector integration. J Virol 88:8 (2014), 4504–4513.
10. Marini, B., Kertesz-Farkas, A., Ali, H., et al. Nuclear architecture dictates HIV-1 integration site selection. Nature 521:7551 (2015), 227–231.
11. Naldini, L., Gene therapy returns to centre stage. Nature 526:7573 (2015), 351–360.
12. Wilber, A., Nienhuis, A.W., Persons, D.A., Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities. Blood 117:15 (2011), 3945–3953.
13. Smith, E.C., Orkin, S.H., Hemoglobin genetics: recent contributions of GWAS and gene editing. Hum Mol Genet 25:R2 (2016), R99–R105.
14. Rivella, S., Sadelain, M., Genetic treatment of severe hemoglobinopathies: the combat against transgene variegation and transgene silencing. Semin Hematol 35:2 (1998), 112–125.
15. May, C., Rivella, S., Callegari, J., et al. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 406:6791 (2000), 82–86.
16. Pawliuk, R., Westerman, K.A., Fabry, M.E., et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science 294:5550 (2001), 2368–2371.
17. May, C., Rivella, S., Chadburn, A., et al. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood 99:6 (2002), 1902–1908.
18. Rivella, S., May, C., Chadburn, A., et al. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta-globin gene transfer. Blood 101:8 (2003), 2932–2939.
19. Negre, O., Bartholomae, C., Beuzard, Y., et al. Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of beta-thalassemia and sickle cell disease. Curr Gene Ther 15:1 (2015), 64–81.
20. Miccio, A., Cesari, R., Lotti, F., et al. In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of beta-thalassemia. Proc Natl Acad Sci U S A 105:30 (2008), 10547–10552.
21. Roselli, E.A., Mezzadra, R., Frittoli, M.C., et al. Correction of beta-thalassemia major by gene transfer in haematopoietic progenitors of pediatric patients. EMBO Mol Med 2:8 (2010), 315–328.
22. Emery, D.W., Yannaki, E., Tubb, J., et al. A chromatin insulator protects retrovirus vectors from chromosomal position effects. Proc Natl Acad Sci U S A 97:16 (2000), 9150–9155.
23. Arumugam, P.I., Scholes, J., Perelman, N., et al. Improved human beta-globin expression from self-inactivating lentiviral vectors carrying the chicken hypersensitive site-4 (cHS4) insulator element. Mol Ther 15:10 (2007), 1863–1871.
24. Romero, Z., Urbinati, F., Geiger, S., et al. beta-globin gene transfer to human bone marrow for sickle cell disease. J Clin Invest 123:8 (2013), 3317–3330.
25. Negre, O., Eggimann, A.V., Beuzard, Y., et al. Gene therapy of the beta-hemoglobinopathies by lentiviral transfer of the beta(A(T87Q))-globin gene. Hum Gene Ther 27:2 (2016), 148–165.
26. Higgs, D.R., Engel, J.D., Stamatoyannopoulos, G., Thalassaemia. Lancet 379:9813 (2012), 373–383.
27. Weatherall, D.J., The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev 26:Suppl 1 (2012), S3–S6.
28. Chang, Y.P., Littera, R., Garau, R., et al. The role of heterocellular hereditary persistence of fetal haemoglobin in beta(0)-thalassaemia intermedia. Br J Haematol 114:4 (2001), 899–906.
29. Panigrahi, I., Agarwal, S., Genetic determinants of phenotype in beta-thalassemia. Hematology 13:4 (2008), 247–252.
30. Rund, D., Rachmilewitz, E., Beta-thalassemia. N Engl J Med 353:11 (2005), 1135–1146.
31. Vento, S., Cainelli, F., Cesario, F., Infections and thalassaemia. Lancet Infect Dis 6:4 (2006), 226–233.
32. Borgna-Pignatti, C., The life of patients with thalassemia major. Haematologica 95:3 (2010), 345–348.
33. Angelucci, E., Hematopoietic stem cell transplantation in thalassemia. Hematol Am Soc Hematol Educ Program 2010 (2010), 456–462.
34. Chiesa, R., Cappelli, B., Crocchiolo, R., et al. Unpredictability of intravenous busulfan pharmacokinetics in children undergoing hematopoietic stem cell transplantation for advanced beta thalassemia: limited toxicity with a dose-adjustment policy. Biol Blood Marrow Transplant 16:5 (2010), 622–628.
35. Lucarelli, G., Gaziev, J., Advances in the allogeneic transplantation for thalassemia. Blood Rev 22:2 (2008), 53–63.
36. Akinsheye, I., Alsultan, A., Solovieff, N., et al. Fetal hemoglobin in sickle cell anemia. Blood 118:1 (2011), 19–27.
37. Bernardo, M., Piras, E., Vacca, A., et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood 120:122 (2012), 473–476.
38. La Nasa, G., Caocci, G., Argiolu, F., et al. Unrelated donor stem cell transplantation in adult patients with thalassemia. Bone Marrow Transplant 36:11 (2005), 971–975.
39. Ruggeri, A., Eapen, M., Scaravadou, A., et al. Umbilical cord blood transplantation for children with thalassemia and sickle cell disease. Biol Blood Marrow Transplant 17:9 (2011), 1375–1382.
40. Angelucci, E., Matthes-Martin, S., Baronciani, D., et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica 99:5 (2014), 811–820.
41. Eldor, A., Rachmilewitz, E.A., The hypercoagulable state in thalassemia. Blood 99:1 (2002), 36–43.
42. Taher, A.T., Otrock, Z.K., Uthman, I., et al. Thalassemia and hypercoagulability. Blood Rev 22:5 (2008), 283–292.
43. De Clercq, E., The bicyclam AMD3100 story. Nat Rev Drug Discov 2:7 (2003), 581–587.
44. DiPersio, J.F., Stadtmauer, E.A., Nademanee, A., et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 113:23 (2009), 5720–5726.
45. Yannaki, E., Karponi, G., Zervou, F., et al. Hematopoietic stem cell mobilization for gene therapy: superior mobilization by the combination of granulocyte-colony stimulating factor plus plerixafor in patients with beta-thalassemia major. Hum Gene Ther 24:10 (2013), 852–860.
46. Yannaki, E., Papayannopoulou, T., Jonlin, E., et al. Hematopoietic stem cell mobilization for gene therapy of adult patients with severe beta-thalassemia: results of clinical trials using G-CSF or plerixafor in splenectomized and nonsplenectomized subjects. Mol Ther 20:1 (2012), 230–238.
47. Karponi, G., Psatha, N., Lederer, C.W., et al. Plerixafor+G-CSF-mobilized CD34+ cells represent an optimal graft source for thalassemia gene therapy. Blood 126:5 (2015), 616–619.
48. Lidonnici, M.R., Aprile, A., Frittoli, M.C., et al. Plerixafor and G-CSF combination mobilizes hematopoietic stem and progenitors cells with a distinct transcriptional profile and a reduced in vivo homing capacity compared to Plerixafor alone. Haematologica 102:4 (2017), e120–e124.
49. Sessa, M., Lorioli, L., Fumagalli, F., et al. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet 388:10043 (2016), 476–487.
50. Mansilla-Soto, J., Riviere, I., Boulad, F., et al. Cell and gene therapy for the beta-thalassemias: advances and prospects. Hum Gene Ther 27:4 (2016), 295–304.
51. Aiuti, A., Naldini, L., Safer conditioning for blood stem cell transplants. Nat Biotechnol 34:7 (2016), 721–723.
52. Aprile, A.L.M., Gulino, A., Tripodo, C., et al. Alteration of HSC functions in thalassemia. Blood, 126, 2015, 4752.
53. Imren, S., Payen, E., Westerman, K.A., et al. Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells. Proc Natl Acad Sci U S A 99:22 (2002), 14380–14385.
54. Hanawa, H., Hargrove, P.W., Kepes, S., et al. Extended beta-globin locus control region elements promote consistent therapeutic expression of a gamma-globin lentiviral vector in murine beta-thalassemia. Blood 104:8 (2004), 2281–2290.
55. Persons, D.A., Allay, E.R., Sawai, N., et al. Successful treatment of murine {beta}-thalassemia using in vivo selection of genetically-modified, drug-resistant hematopoietic stem cells. Blood 102:2 (2003), 506–516.
56. Lisowski, L., Sadelain, M., Locus control region elements HS1 and HS4 enhance the therapeutic efficacy of globin gene transfer in beta-thalassemic mice. Blood 110:13 (2007), 4175–4178.
57. Miccio, A., Poletti, V., Tiboni, F., et al. The GATA1-HS2 enhancer allows persistent and position-independent expression of a beta-globin transgene. PLoS One, 6(12), 2011, e27955.
58. Breda, L., Casu, C., Gardenghi, S., et al. Therapeutic hemoglobin levels after gene transfer in beta-thalassemia mice and in hematopoietic cells of beta-thalassemia and sickle cells disease patients. PLoS One, 7(3), 2012, e32345.
59. Puthenveetil, G., Scholes, J., Carbonell, D., et al. Successful correction of the human beta-thalassemia major phenotype using a lentiviral vector. Blood 104:12 (2004), 3445–3453.
60. Lidonnici, M., Salvatori, F., Tiboni, F., et al. High dose of transduced HPSCs provides safe long term correction of beta-thalassemia. Hum Gene Ther, 24(12), 2013, A109.
61. Moiani, A., Paleari, Y., Sartori, D., et al. Lentiviral vector integration in the human genome induces alternative splicing and generates aberrant transcripts. J Clin Invest 122:5 (2012), 1653–1666.
62. Cavazzana-Calvo, M., Payen, E., Negre, O., et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 467:7313 (2010), 318–322.
63. Thompson, A.A., Kwiatkowski, J., Rasko, J., et al. Lentiglobin gene therapy for transfusion-dependent β-thalassemia: update from the Northstar Hgb-204 phase 1/2 clinical study. Blood, 128, 2016, 1165.
64. Marktel, S.G.F., Cicalese, M.P., Casiraghi, M., et al. A phase I/II study of autologous hematopoietic stem cells genetically modified with globe lentiviral vector for the treatment of transfusion dependent beta-thalassemia. Haematologica, 101(s1), 2016, 168.
65. Madigan, C., Malik, P., Pathophysiology and therapy for haemoglobinopathies. Part I: sickle cell disease. Expert Rev Mol Med 8:9 (2006), 1–23.
66. Platt, O.S., Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 358:13 (2008), 1362–1369.
67. Piel, F.B., Patil, A.P., Howes, R.E., et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet 381:9861 (2013), 142–151.
68. Zhang, D., Xu, C., Manwani, D., et al. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood 127:7 (2016), 801–809.
69. Fitzhugh, C.D., Hsieh, M.M., Bolan, C.D., et al. Granulocyte colony-stimulating factor (G-CSF) administration in individuals with sickle cell disease: time for a moratorium?. Cytotherapy 11:4 (2009), 464–471.
70. Steinberg, M.H., Chui, D.H., Dover, G.J., et al. Fetal hemoglobin in sickle cell anemia: a glass half full?. Blood 123:4 (2014), 481–485.
71. Pestina, T.I., Hargrove, P.W., Jay, D., et al. Correction of murine sickle cell disease using gamma-globin lentiviral vectors to mediate high-level expression of fetal hemoglobin. Mol Ther 17:2 (2009), 245–252.
72. Perumbeti, A., Higashimoto, T., Urbinati, F., et al. A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction. Blood 114:6 (2009), 1174–1185.
73. McCune, S.L., Reilly, M.P., Chomo, M.J., et al. Recombinant human hemoglobins designed for gene therapy of sickle cell disease. Proc Natl Acad Sci U S A 91:21 (1994), 9852–9856.
74. Levasseur, D.N., Ryan, T.M., Reilly, M.P., et al. A recombinant human hemoglobin with anti-sickling properties greater than fetal hemoglobin. J Biol Chem 279:26 (2004), 27518–27524.
75. Levasseur, D.N., Ryan, T.M., Pawlik, K.M., et al. Correction of a mouse model of sickle cell disease: lentiviral/antisickling beta-globin gene transduction of unmobilized, purified hematopoietic stem cells. Blood 102:13 (2003), 4312–4319.
76. Urbinati, F., Hargrove, P.W., Geiger, S., et al. Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells. Exp Hematol 43:5 (2015), 346–351.
77. Andreani, M., Testi, M., Gaziev, J., et al. Quantitatively different red cell/nucleated cell chimerism in patients with long-term, persistent hematopoietic mixed chimerism after bone marrow transplantation for thalassemia major or sickle cell disease. Haematologica 96:1 (2011), 128–133.
78. Walters, M.C., Patience, M., Leisenring, W., et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 7:12 (2001), 665–673.
79. Wu, C.J., Gladwin, M., Tisdale, J., et al. Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis. Br J Haematol 139:3 (2007), 504–507.
80. Ribeil, J.A., Hacein-Bey-Abina, S., Payen, E., et al. Gene therapy in a patient with sickle cell disease. N Engl J Med 376:9 (2017), 848–855.
81. Kanter, J., Walters, M.C., Hsieh, M.M., et al. Interim results from a phase 1/2 clinical study of lentiglobin gene therapy for severe sickle cell disease. Blood, 128(1176), 2016.
82. Hoban, M.D., Cost, G.J., Mendel, M.C., et al. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells. Blood 125:17 (2015), 2597–2604.
83. Hoban, M.D., Lumaquin, D., Kuo, C.Y., et al. CRISPR/Cas9-mediated correction of the sickle mutation in human CD34+ cells. Mol Ther 24:9 (2016), 1561–1569.
84. DeWitt, M.A., Magis, W., Bray, N.L., et al. Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells. Sci Transl Med, 8(360), 2016, 360ra134.
85. Dever, D.P., Bak, R.O., Reinisch, A., et al. CRISPR/Cas9 beta-globin gene targeting in human haematopoietic stem cells. Nature 539:7629 (2016), 384–389.
86. Bauer, D.E., Orkin, S.H., Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev 33 (2015), 62–70.
87. Brendel, C., Guda, S., Renella, R., et al. Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. J Clin Invest 126:10 (2016), 3868–3878.
88. Tsang, J.C., Yu, Y., Burke, S., et al. Single-cell transcriptomic reconstruction reveals cell cycle and multi-lineage differentiation defects in Bcl11a-deficient hematopoietic stem cells. Genome Biol, 16, 2015, 178.
89. + hematopoietic stem and progenitor cells. Mol Ther Methods Clin Dev 4 (2017), 137–148.
90. Canver, M.C., Smith, E.C., Sher, F., et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature 527:7577 (2015), 192–197.
91. Vierstra, J., Reik, A., Chang, K.-H., et al. Functional footprinting of regulatory DNA. Nat Meth 12:10 (2015), 927–930.
92. Traxler, E.A., Yao, Y., Wang, Y.-D., et al. A genome-editing strategy to treat [beta]-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med 22:9 (2016), 987–990.
93. Ye, L., Wang, J., Tan, Y., et al. Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: an approach for treating sickle cell disease and beta-thalassemia. Proc Natl Acad Sci U S A 113:38 (2016), 10661–10665.
94. Genovese, P., Schiroli, G., Escobar, G., et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature 510:7504 (2014), 235–240.
95. Breda, L., Motta, I., Lourenco, S., et al. Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers. Blood 128:8 (2016), 1139–1143.