Gene therapy of chronic granulomatous disease: The engraftment dilemma

Molecular Therapy

Volumn 19, Issue 1, 2011, Pages 28-35

  Grez, Manuel ^a   Reichenbach, Janine ^b   Schwäble, Joachim ^a,c   Seger, Reinhard ^b   Dinauer, Mary C ^d   Thrasher, Adrian J ^e,f  

^a INSTITUTE FOR TUMOR BIOLOGY AND EXPERIMENTAL THERAPY   (Germany)

^b UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

^c UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^d INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

^f GREAT ORMOND STREET HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BUSULFAN; FLUDARABINE; LENTIVIRUS VECTOR; MELPHALAN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; RETROVIRUS VECTOR;

ADENOSINE DEAMINASE DEFICIENCY; ARTICLE; BONE MARROW TRANSPLANTATION; CELL BASED GENE THERAPY; CHRONIC GRANULOMATOUS DISEASE; ENGRAFTMENT; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; MYELOABLATIVE CONDITIONING; NONHUMAN; NONMYELOABLATIVE CONDITIONING; REDUCED INTENSITY CONDITIONING; SINGLE DRUG DOSE; STEM CELL MOBILIZATION; WISKOTT ALDRICH SYNDROME;

EID: 78650922808     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2010.232     Document Type: Review

References (125)

1. Roos, D (1994). The genetic basis of chronic granulomatous disease. Immunol Rev 138: 121-157. (Pubitemid 24147419)
2. Segal, AW (1996). The NADPH oxidase and chronic granulomatous disease. Mol Med Today 2: 129-135.
3. Segal, BH, Leto, TL, Gallin, JI, Malech, HL and Holland, SM (2000). Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 79: 170-200.
4. Holland, SM (2010). Chronic granulomatous disease. Clin Rev Allergy Immunol 38: 3-10.
5. Van den Berg, JM, Van Koppen, E, Ahlin, A, Belohradsky, BH, Bernatowska, E, Corbeel, L et al. (2009). Chronic granulomatous disease: the European experience. PLoS ONE 4: e5234.
6. Babior, BM (2004). NADPH oxidase. Curr Opin Immunol 16: 42-47.
7. Dinauer, MC (2005). Chronic granulomatous disease and other disorders of phagocyte function. Hematology Am Soc Hematol Educ Program: 89-95.
8. Heyworth, PG, Cross, AR and Curnutte, JT (2003). Chronic granulomatous disease. Curr Opin Immunol 15: 578-584.
9. Kang, EM and Malech, HL (2009). Advances in treatment for chronic granulomatous disease. Immunol Res 43: 77-84.
10. Segal, AW (2005). How neutrophils kill microbes. Annu Rev Immunol 23: 197-223.
11. Brinkmann, V, Reichard, U, Goosmann, C, Fauler, B, Uhlemann, Y, Weiss, DS et al. (2004). Neutrophil extracellular traps kill bacteria. Science 303: 1532-1535.
12. Urban, CF, Reichard, U, Brinkmann, V and Zychlinsky, A (2006). Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol 8: 668-676.
13. Fuchs, TA, Abed, U, Goosmann, C, Hurwitz, R, Schulze, I, Wahn, V et al. (2007). Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176: 231-241.
14. Abo, A, Pick, E, Hall, A, Totty, N, Teahan, CG and Segal, AW (1991). Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature 353: 668-670.
15. Knaus, UG, Heyworth, PG, Evans, T, Curnutte, JT and Bokoch, GM (1991). Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 254: 1512-1515.
16. Yamauchi, A, Marchal, CC, Molitoris, J, Pech, N, Knaus, U, Towe, J et al. (2005). Rac GTPase isoform-specifc regulation of NADPH oxidase and chemotaxis in murine neutrophils in vivo. Role of the C-terminal polybasic domain. J Biol Chem 280: 953-964.
17. Matute, JD, Arias, AA, Wright, NA, Wrobel, I, Waterhouse, CC, Li, XJ et al. (2009). A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood 114: 3309-3315.
18. Winkelstein, JA, Marino, MC, Johnston, RB Jr, Boyle, J, Curnutte, J, Gallin, JI et al. (2000). Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79: 155-169.
19. Brown, JR, Goldblatt, D, Buddle, J, Morton, L and Thrasher, AJ (2003). Diminished production of anti-infammatory mediators during neutrophil apoptosis and macrophage phagocytosis in chronic granulomatous disease (CGD). J Leukoc Biol 73: 591-599.
20. Morgenstern, DE, Gifford, MA, Li, LL, Doerschuk, CM and Dinauer, MC (1997). Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and infammatory response to Aspergillus fumigatus. J Exp Med 185: 207-218.
21. Rosenzweig, SD (2008). Infammatory manifestations in chronic granulomatous disease (CGD). J Clin Immunol 28 Suppl 1: S67-S72.
22. Schäppi, MG, Jaquet, V, Belli, DC and Krause, KH (2008). Hyperinfammation in chronic granulomatous disease and anti-infammatory role of the phagocyte NADPH oxidase. Semin Immunopathol 30: 255-271.
23. Seger, RA (2008). Modern management of chronic granulomatous disease. Br J Haematol 140: 255-266.
24. Seger, RA, Gungor, T, Belohradsky, BH, Blanche, S, Bordigoni, P, Di Bartolomeo, P et al. (2002). Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodifed hemopoietic allograft: a survey of the European experience, 1985-2000. Blood 100: 4344-4350.
25. Royer-Pokora, B, Kunkel, LM, Monaco, AP, Goff, SC, Newburger, PE, Baehner, RL et al. (1986). Cloning the gene for an inherited human disorder-chronic granulomatous disease-on the basis of its chromosomal location. Nature 322: 32-38. (Pubitemid 16061506)
26. Lambeth, JD (2004). NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4: 181-189.
27. Martire, B, Rondelli, R, Soresina, A, Pignata, C, Broccoletti, T, Finocchi, A et al.; IPINET. (2008). Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol 126: 155-164.
28. Jones, LB, McGrogan, P, Flood, TJ, Gennery, AR, Morton, L, Thrasher, A et al. (2008). Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol 152: 211-218.
29. Woodman, RC, Newburger, PE, Anklesaria, P, Erickson, RW, Rae, J, Cohen, MS et al. (1995). A new X-linked variant of chronic granulomatous disease characterized by the existence of a normal clone of respiratory burst-competent phagocytic cells. Blood 85: 231-241.
30. rd, Jackson, SH, Spratt, SK, Li, F, Holland, SM and Malech, HL (1997). Enhanced host defense after gene transfer in the murine p47phox-defcient model of chronic granulomatous disease. Blood 89: 2268-2275.
31. rd, Harbeck, RJ and Johnston, RB Jr (1985). Recurrent severe infections in a girl with apparently variable expression of mosaicism for chronic granulomatous disease. J Pediatr 106: 50-55.
32. Rex, JH, Bennett, JE, Gallin, JI, Malech, HL and Melnick, DA (1990). Normal and defcient neutrophils can cooperate to damage Aspergillus fumigatus hyphae. J Infect Dis 162: 523-528.
33. Malech, HL, Maples, PB, Whiting-Theobald, N, Linton, GF, Sekhsaria, S, Vowells, SJ et al. (1997). Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci USA 94: 12133-12138.
34. + cells. Blood 92(suppl 1): 690a.
35. Malech H, Horwitz M, Whiting-Theobald N, Linton G, Miller J, Holland S et al. (2000). Multiple cycles of ex-vivo gene therapy for X-linked chronic granulomatous disease (CGD) sustain production of oxidase-normal peripheral blood neutrophils. Mol Ther 1(5 Suppl): S146.
36. Goebel, WS and Dinauer, MC (2003). Gene therapy for chronic granulomatous disease. Acta Haematol 110: 86-92.
37. Kang, EM, Choi, U, Theobald, N, Linton, G, Long Priel, DA, Kuhns, D et al. (2010). Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. Blood 115: 783-791.
38. Stein, S, Ott, MG, Schultze-Strasser, S, Jauch, A, Burwinkel, B, Kinner, A et al. (2010). Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med 16: 198-204.
39. Bianchi, M, Hakkim, A, Brinkmann, V, Siler, U, Seger, RA, Zychlinsky, A et al. (2009). Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood 114: 2619-2622.
40. Ott, MG, Schmidt, M, Schwarzwaelder, K, Stein, S, Siler, U, Koehl, U et al. (2006). Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med 12: 401-409.
41. Thrasher, AJ, Hacein-Bey-Abina, S, Gaspar, HB, Blanche, S, Davies, EG, Parsley, K et al. (2005). Failure of SCID-X1 gene therapy in older patients. Blood 105: 4255-4257.
42. + (memory T) cells in patients with chronic granulomatous disease. J Infect Dis 167: 983-985.
43. Fulcher, DA and Basten, A (1997). B cell life span: a review. Immunol Cell Biol 75: 446-455.
44. Kim JG, Ahn HS, Kang HJ, Kim S, Hong YT, Joo CW et al. (2008). Retroviral gene therapy for X-linked chronic granulomatous disease: results from Phase I/II trial. Blood 112: Abstract 2349.
45. Björgvinsdóttir, H, Ding, C, Pech, N, Gifford, MA, Li, LL and Dinauer, MC (1997). Retroviral-mediated gene transfer of gp91phox into bone marrow cells rescues defect in host defense against Aspergillus fumigatus in murine X-linked chronic granulomatous disease. Blood 89: 41-48.
46. Dinauer, MC, Gifford, MA, Pech, N, Li, LL and Emshwiller, P (2001). Variable correction of host defense following gene transfer and bone marrow transplantation in murine X-linked chronic granulomatous disease. Blood 97: 3738-3745.
47. Goebel, WS, Mark, LA, Billings, SD, Meyers, JL, Pech, N, Travers, JB et al. (2005). Gene correction reduces cutaneous infammation and granuloma formation in murine X-linked chronic granulomatous disease. J Invest Dermatol 125: 705-710.
48. Bosticardo, M, Ghosh, A, Du, Y, Jenkins, NA, Copeland, NG and Candotti, F (2009). Self-inactivating retroviral vector-mediated gene transfer induces oncogene activation and immortalization of primary murine bone marrow cells. Mol Ther 17: 1910-1918.
49. Métais, JY and Dunbar, CE (2008). The MDS1-EVI1 gene complex as a retrovirus integration site: impact on behavior of hematopoietic cells and implications for gene therapy. Mol Ther 16: 439-449.
50. Buonamici, S, Li, D, Chi, Y, Zhao, R, Wang, X, Brace, L et al. (2004). EVI1 induces myelodysplastic syndrome in mice. J Clin Invest 114: 713-719.
51. Du, Y, Jenkins, NA and Copeland, NG (2005). Insertional mutagenesis identifes genes that promote the immortalization of primary bone marrow progenitor cells. Blood 106: 3932-3939.
52. Komeno, Y, Kitaura, J and Kitamura, T (2009). Molecular bases of myelodysplastic syndromes: lessons from animal models. J Cell Physiol 219: 529-534.
53. Kustikova, O, Fehse, B, Modlich, U, Yang, M, Düllmann, J, Kamino, K et al. (2005). Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 308: 1171-1174.
54. Laricchia-Robbio, L and Nucifora, G (2008). Signifcant increase of self-renewal in hematopoietic cells after forced expression of EVI1. Blood Cells Mol Dis 40: 141-147.
55. Li, Z, Düllmann, J, Schiedlmeier, B, Schmidt, M, von Kalle, C, Meyer, J et al. (2002). Murine leukemia induced by retroviral gene marking. Science 296: 497.
56. Modlich, U, Navarro, S, Zychlinski, D, Maetzig, T, Knoess, S, Brugman, MH et al. (2009). Insertional transformation of hematopoietic cells by self-inactivating lentiviral and γ-retroviral vectors. Mol Ther 17: 1919-1928.
57. Modlich, U, Schambach, A, Brugman, MH, Wicke, DC, Knoess, S, Li, Z et al. (2008). Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16. Leukemia 22: 1519-1528.
58. Dunbar, CE, Tisdale, J, Yu, JM, Soma, T, Zujewski, J, Bodine, D et al. (1997). Transduction of hematopoietic stem cells in humans and in nonhuman primates. Stem Cells 15 Suppl 1: 135-9; discussion 139.
59. Tisdale, JF, Hanazono, Y, Sellers, SE, Agricola, BA, Metzger, ME, Donahue, RE et al. (1998). Ex vivo expansion of genetically marked rhesus peripheral blood progenitor cells results in diminished long-term repopulating ability. Blood 92: 1131-1141.
60. Dao, M and Nolta, J (1999). Molecular control of cell cycle progression in primary human hematopoietic stem cells: methods to increase levels of retroviral-mediated transduction. Leukemia 13: 1473-1480.
61. Aiuti, A, Slavin, S, Aker, M, Ficara, F, Deola, S, Mortellaro, A et al. (2002). Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296: 2410-2413.
62. Aiuti, A, Cassani, B, Andolf, G, Mirolo, M, Biasco, L, Recchia, A et al. (2007). Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy. J Clin Invest 117: 2233-2240.
63. Aiuti, A, Cattaneo, F, Galimberti, S, Benninghoff, U, Cassani, B, Callegaro, L et al. (2009). Gene therapy for immunodefciency due to adenosine deaminase defciency. N Engl J Med 360: 447-458.
64. Gaspar, HB, Bjorkegren, E, Parsley, K, Gilmour, KC, King, D, Sinclair, J et al. (2006). Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol Ther 14: 505-513.
65. Sokolic, R, Kesserwan, C and Candotti, F (2008). Recent advances in gene therapy for severe congenital immunodefciency diseases. Curr Opin Hematol 15: 375-380.
66. Boztug K, Schmidt M, Schwarzer A, Banerjee P, Avedillo Díez I, Dewey R et al. (2010). Successful hematopoietic stem cell gene therapy for Wiskott-Aldrich Syndrome. New Engl J Med, in press.
67. Rosenzweig, M, MacVittie, TJ, Harper, D, Hempel, D, Glickman, RL, Johnson, RP et al. (1999). Effcient and durable gene marking of hematopoietic progenitor cells in nonhuman primates after nonablative conditioning. Blood 94: 2271-2286.
68. Huhn, RD, Tisdale, JF, Agricola, B, Metzger, ME, Donahue, RE and Dunbar, CE (1999). Retroviral marking and transplantation of rhesus hematopoietic cells by nonmyeloablative conditioning. Hum Gene Ther 10: 1783-1790.
69. Kahl, CA, Tarantal, AF, Lee, CI, Jimenez, DF, Choi, C, Pepper, K et al. (2006). Effects of busulfan dose escalation on engraftment of infant rhesus monkey hematopoietic stem cells after gene marking by a lentiviral vector. Exp Hematol 34: 369-381.
70. Kang, EM, Hsieh, MM, Metzger, M, Krouse, A, Donahue, RE, Sadelain, M et al. (2006). Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modifed hematopoietic stem cells in the rhesus macaque model. Exp Hematol 34: 132-139.
71. Brenner S, Choi U, Whiting-Theobald N, Linton G, Kang E, Rudikoff A et al. (2003). Insertional analyses in rhesus monkey blood cells after non-myeloablative hematopoietic stem cell marking with a RD114-MFGS-gp91phox vector designed for treatment of X-linked chronic granulomatous disease. Blood 102: 102.
72. Arruda, VR, Favaro, P and Finn, JD (2009). Strategies to modulate immune responses: a new frontier for gene therapy. Mol Ther 17: 1492-1503.
73. Dinauer, MC (2003). Regulation of neutrophil function by Rac GTPases. Curr Opin Hematol 10: 8-15.
74. Nauseef, WM (2004). Assembly of the phagocyte NADPH oxidase. Histochem Cell Biol 122: 277-291.
75. Lewis, EM, Sergeant, S, Ledford, B, Stull, N, Dinauer, MC and McPhail, LC (2010). Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. J Biol Chem 285: 2959-2967.
76. Martyn, KD, Kim, MJ, Quinn, MT, Dinauer, MC and Knaus, UG (2005). p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils. Blood 106: 3962-3969.
77. Suh, CI, Stull, ND, Li, XJ, Tian, W, Price, MO, Grinstein, S et al. (2006). The phosphoinositide-binding protein p40phox activates the NADPH oxidase during FcγIIA receptor-induced phagocytosis. J Exp Med 203: 1915-1925.
78. Zhu, Y, Marchal, CC, Casbon, AJ, Stull, N, von Löhneysen, K, Knaus, UG et al. (2006). Deletion mutagenesis of p22phox subunit of favocytochrome b558: identifcation of regions critical for gp91phox maturation and NADPH oxidase activity. J Biol Chem 281: 30336-30346.
79. Piccoli, C, D'Aprile, A, Ripoli, M, Scrima, R, Lecce, L, Boffoli, D et al. (2007). Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species. Biochem Biophys Res Commun 353: 965-972.
80. Piccoli, C, Ria, R, Scrima, R, Cela, O, D'Aprile, A, Boffoli, D et al. (2005). Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity. J Biol Chem 280: 26467-26476.
81. Chen, C, Liu, Y, Liu, R, Ikenoue, T, Guan, KL, Liu, Y et al. (2008). TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med 205: 2397-2408.
82. + progenitor cells preservation by hypoxia. J Biotechnol 130: 455-462.
83. Ito, K, Hirao, A, Arai, F, Takubo, K, Matsuoka, S, Miyamoto, K et al. (2006). Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 12: 446-451.
84. Jang, YY and Sharkis, SJ (2007). A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110: 3056-3063.
85. Lewandowski, D, Barroca, V, Ducongé, F, Bayer, J, Van Nhieu, JT, Pestourie, C et al. (2010). In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution. Blood 115: 443-452.
86. + hematopoietic progenitor cells. Blood 115: 1238-1246.
87. Bylund, J, MacDonald, KL, Brown, KL, Mydel, P, Collins, LV, Hancock, RE et al. (2007). Enhanced infammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-KB. Eur J Immunol 37: 1087-1096.
88. Romani, L, Fallarino, F, De Luca, A, Montagnoli, C, D'Angelo, C, Zelante, T et al. (2008). Defective tryptophan catabolism underlies infammation in mouse chronic granulomatous disease. Nature 451: 211-215.
89. Baldridge, MT, King, KY, Boles, NC, Weksberg, DC and Goodell, MA (2010). Quiescent haematopoietic stem cells are activated by IFN-y in response to chronic infection. Nature 465: 793-797.
90. Dybedal, I, Bryder, D, Fossum, A, Rusten, LS and Jacobsen, SE (2001). Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells. Blood 98: 1782-1791.
91. Essers, MA, Offner, S, Blanco-Bose, WE, Waibler, Z, Kalinke, U, Duchosal, MA et al. (2009). IFNcc activates dormant haematopoietic stem cells in vivo. Nature 458: 904-908.
92. Dinauer, MC, Li, LL, Björgvinsdóttir, H, Ding, C and Pech, N (1999). Long-term correction of phagocyte NADPH oxidase activity by retroviral-mediated gene transfer in murine X-linked chronic granulomatous disease. Blood 94: 914-922.
93. Goebel, WS and Dinauer, MC (2002). Retroviral-mediated gene transfer and nonmyeloablative conditioning: studies in a murine X-linked chronic granulomatous disease model. J Pediatr Hematol Oncol 24: 787-790.
94. + cells from patients with X-linked chronic granulomatous disease. Blood 100: 4381-4390.
95. + cells. Blood 102: 2789-2797.
96. Sadat, MA, Pech, N, Saulnier, S, Leroy, BA, Hossle, JP, Grez, M et al. (2003). Long-term high-level reconstitution of NADPH oxidase activity in murine X-linked chronic granulomatous disease using a bicistronic vector expressing gp91phox and a ALNGFR cell surface marker. Hum Gene Ther 14: 651-666.
97. Goebel, WS, Pech, NK and Dinauer, MC (2004). Stable long-term gene correction with low-dose radiation conditioning in murine X-linked chronic granulomatous disease. Blood Cells Mol Dis 33: 365-371.
98. Brenner, S, Ryser, MF, Choi, U, Whiting-Theobald, N, Kuhlisch, E, Linton, G et al. (2006). Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after nonmyeloablative transplantation with transduced autologous peripheral blood progenitor cells. Mol Ther 14: 202-211.
99. Naumann, N, De Ravin, SS, Choi, U, Moayeri, M, Whiting-Theobald, N, Linton, GF et al. (2007). Simian immunodefciency virus lentivector corrects human X-linked chronic granulomatous disease in the NOD/SCID mouse xenograft. Gene Ther 14: 1513-1524.
100. Moreno-Carranza, B, Gentsch, M, Stein, S, Schambach, A, Santilli, G, Rudolf, E et al. (2009). Transgene optimization signifcantly improves SIN vector titers, gp91phox expression and reconstitution of superoxide production in X-CGD cells. Gene Ther 16: 111-118.
101. Sadat, MA, Dirscherl, S, Sastry, L, Dantzer, J, Pech, N, Griffn, S et al. (2009). Retroviral vector integration in post-transplant hematopoiesis in mice conditioned with either submyeloablative or ablative irradiation. Gene Ther 16: 1452-1464.
102. Schuetz, C, Hoenig, M, Gatz, S, Speth, F, Benninghoff, U, Schulz, A et al. (2009). Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease. Immunol Res 44: 35-41.
103. Thrasher, A and Goldblatt, D (2001). Hematopoietic-cell transplantation for chronic granulomatous disease. N Engl J Med 345: 377-378.
104. Montini, E, Cesana, D, Schmidt, M, Sanvito, F, Ponzoni, M, Bartholomae, C et al. (2006). Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol 24: 687-696.
105. Salmon, P and Trono, D (2002). Lentiviral vectors for the gene therapy of lympho-hematological disorders. Curr Top Microbiol Immunol 261: 211-227.
106. Schambach, A and Baum, C (2008). Clinical application of lentiviral vectors-concepts and practice. Curr Gene Ther 8: 474-482.
107. Woods, NB, Ooka, A and Karlsson, S (2002). Development of gene therapy for hematopoietic stem cells using lentiviral vectors. Leukemia 16: 563-569.
108. Consiglio, A, Quattrini, A, Martino, S, Bensadoun, JC, Dolcetta, D, Trojani, A et al. (2001). In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Nat Med 7: 310-316.
109. Ginn, SL, Liao, SH, Dane, A P, Hu, M, Hyman, J, Finnie, JW et al. (2010). Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and γc overexpression. Mol Ther 18: 965-976.
110. Mortellaro, A, Hernandez, RJ, Guerrini, MM, Carlucci, F, Tabucchi, A, Ponzoni, M et al. (2006). Ex vivo gene therapy with lentiviral vectors rescues adenosine deaminase (ADA)-defcient mice and corrects their immune and metabolic defects. Blood 108: 2979-2988.
111. Galy, A, Roncarolo, MG and Thrasher, AJ (2008). Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther 8: 181-190.
112. Mátrai, J, Chuah, MK and VandenDriessche, T (2010). Recent advances in lentiviral vector development and applications. Mol Ther 18: 477-490.
113. Qasim, W, Gaspar, HB and Thrasher, AJ (2009). Progress and prospects: gene therapy for inherited immunodefciencies. Gene Ther 16: 1285-1291.
114. González-Murillo, A, Lozano, ML, Alvarez, L, Jacome, A, Almarza, E, Navarro, S et al. (2010). Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with Fanconi anemia. Hum Gene Ther 21: 623-630.
115. Friedman, AD (2007). Transcriptional control of granulocyte and monocyte development. Oncogene 26: 6816-6828.
116. Rosmarin, AG, Yang, Z and Resendes, KK (2005). Transcriptional regulation in myelopoiesis: hematopoietic fate choice, myeloid differentiation, and leukemogenesis. Exp Hematol 33: 131-143.
117. Rosenbauer, F and Tenen, DG (2007). Transcription factors in myeloid development: balancing differentiation with transformation. Nat Rev Immunol 7: 105-117.
118. Amendola, M, Passerini, L, Pucci, F, Gentner, B, Bacchetta, R and Naldini, L (2009). Regulated and multiple miRNA and siRNA delivery into primary cells by a lentiviral platform. Mol Ther 17: 1039-1052.
119. Brown, BD and Naldini, L (2009). Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 10: 578-585.
120. Cartier, N, Hacein-Bey-Abina, S, Bartholomae, CC, Veres, G, Schmidt, M, Kutschera, I et al. (2009). Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326: 818-823.
121. Beard, BC, Trobridge, GD, Ironside, C, McCune, JS, Adair, JE and Kiem, HP (2010). Effcient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates. J Clin Invest 120: 2345-2354.
122. Czechowicz, A, Kraft, D, Weissman, IL and Bhattacharya, D (2007). Effcient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science 318: 1296-1299.
123. Buchmann, I, Meyer, RG, Mier, W and Haberkorn, U (2009). Myeloablative radioimmunotherapy in conditioning prior to haematological stem cell transplantation: closing the gap between beneft and toxicity? Eur J Nucl Med Mol Imaging 36: 484-498.
124. Zhang, MM and Gopal, AK (2008). Radioimmunotherapy-based conditioning regimens for stem cell transplantation. Semin Hematol 45: 118-125.
125. Xue, X, Pech, NK, Shelley, WC, Srour, EF, Yoder, MC and Dinauer, MC (2010). Antibody targeting KIT as pre-transplant conditioning in immunocompetent mice. Blood (epub ahead of print).