Development of gene therapy for blood disorders

Blood

Volumn 111, Issue 9, 2008, Pages 4431-4444

  Nienhuis, Arthur W ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; HEMOGLOBIN; RECOMBINANT DNA;

ARTICLE; BLOOD DISEASE; CANCER CHEMOTHERAPY; CLINICAL TRIAL; DRUG EFFICACY; DRUG TARGETING; GENE THERAPY; GENE TRANSFER; GENE VECTOR; GENOTOXICITY; GRAFT VERSUS HOST REACTION; GRANULOMATOSIS; HEMATOLOGIC MALIGNANCY; HEMATOPOIETIC CELL; HEMOPHILIA; HUMAN; LEUKEMIA; LYMPHOMA; NONHUMAN; PRIORITY JOURNAL; RETROVIRUS; SEVERE COMBINED IMMUNODEFICIENCY; SUICIDE GENE THERAPY; TUMOR VIRUS; VIRUS INFECTION; ANIMAL; HEMATOLOGIC DISEASE; METHODOLOGY; REVIEW; TREATMENT OUTCOME;

ANIMALS; GENE THERAPY; GENETIC VECTORS; HEMATOLOGIC DISEASES; HUMANS; TREATMENT OUTCOME;

EID: 44849127181     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2007-11-078121     Document Type: Article

References (154)

1. Anderson WF. Genetic therapy. In: Hamilton M, ed. The New Genetics and the Future of Man. Grand Rapids, MI: Eerdmans, 1972:109-124.
2. Friedmann T, Roblin R. Gene therapy for human genetic disease? Science. 1972;175:949-955.
3. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science. 2000;288:669-672.
4. Hacein-Bey-Abina S, Le Deist F, Carlier F, et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med. 2002;346:1185-1193.
5. Gaspar HB, Parsley KL, Howe S, et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet. 2004;364:2181-2187.
6. Aiuti ASlavin S, Aker M, et al. Correction of ADASCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science. 2002; 296:2410-2413.
7. Rosenberg SA, Aebersold P, Cornetta K, et al. Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumorinfiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990;323:570-578.
8. Blaese RM, Culver KW, Miller AD, et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science. 1995; 270:475-480.
9. Pinkel D. Treatment of childhood acute lymphocytic leukemia. J Pediatr. 1970;77:1089-1091.
10. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354:166-178.
11. Gatti RA, Meuwissen JH, Allen HD, Hong R, Good RA. Immunological reconstitution of sexlinked lymphopenic immunological deficiency. Lancet. 1968;2:1366-1369.
12. Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Lancet. 1968; 2:1364-1366.
13. Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med. 2007;357:1472-1475.
14. Varmus H. Retroviruses. Science. 1988;240:1427-1435.
15. Baltimore D. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature. 1970;226:1209-1211.
16. Temin HM, Mizutani S. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature. 1970;226:1211-1213.
17. Maniatis T, Kee SG, Efstratiadis A, Kafatos FC. Amplification and characterization of a betaglobin gene synthesized in vitro. Cell. 1976;8:163-182.
18. Maniatis T, Hardison RC, Lacy E, et al. The isolation of structural genes from libraries of eukaryotic DNA. Cell. 1978;15:687-701.
19. Pellicer A, Wigler M, Axel R, Silverstein S. The transfer and stable integration of the HSV thymidine kinase gene into mouse cells. Cell. 1978;14:133-141.
20. Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973;52:456-467.
21. Anderson WK, Killos L, Sanders-Haigh L, Kretschmer PJ, Diacumakos EG. Replication and expression of thymidine kinase and human globin gene microinjected into mouse fibroblasts. Proc Natl Acad Sci U S A. 1980;77:5399-5403.
22. Capecchi MR. High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell. 1980;22:479-488.
23. Cline MJ, Stang H, Mercola K, et al. Gene transfer in intact animals. Nature. 1980;284:422-425.
24. Joyner A, Keller G, Phillips RA, Bernstein A. Retrovirus transfer of a bacterial gene into mouse haematopoietic progenitor cells. Nature. 1983; 305:556-558.
25. Miller AD, Jolly DJ, Friedmann T, Vema IM. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT. Proc Natl Acad Sci U S A. 1983;80:4709-4713.
26. Mann R, Mulligan RC, Baltimore D. Constuction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983;33:153-159.
27. Watanabe S, Temin HM. Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors. Mol Cell Biol. 1983;3:2241-2249.
28. Markowitz D, Goff S, Bank A. A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol. 1988;62:1120-1124.
29. Markowitz D, Goff S, Bank A. Construction and use of a safe and efficient amphotrophic packaging cell line. Virology. 1988;167:400-406.
30. Williams DA, Lemischka IR, Nathan DG, Mulligan RC. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature. 1984;310:476-480.
31. Till JE, McCulloch EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961;14:213-222.
32. Eglitis MA, Kantoff P, Gilboa E, Anderson WF. Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science. 1985; 230:1395-1398.
33. Dick JE, Magli MC, Huszar D, Phillips R, Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985;42:71-79.
34. Van Doren K, Hanahan D, Gluzman Y. Infection of eucaryotic cells by helper-independent recombinant adenoviruses: early region 1 is not obligatory for integration of viral DNA. J Virol. 1984;50:606-614.
35. Tratschin JD, West MH, Sandbank T, Carter BJ. A human parvovirus, adeno-associated virus, as a eukaryotic vector: transient expression and encapsidation of the prokaryotic gene for chloramphenical acetyltransferase. Mol Cell Biol. 1984;4:2072-2081.
36. Hermonat PL, Muzyczka N. Use of adenoassociated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells. Proc Natl Acad Sci U S A. 1984;81:6466-6470.
37. Naldini L, Blomer U, Gallay P, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272:263-267.
38. Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med. 2001;7:33-40.
39. Russell DW, Miller AD. Foamy virus vectors. J Virol. 1996;70:217-222.
40. Costantini F, Lacy E. Introduction of a rabbit β-globin gene into the mouse germ line. Nature. 1981;294:92-94.
41. Wagner TE, Hoppe PC, Jollick JD, Scholl DR, Hodinka RL, Gault JB. Microinjection of a rabbit β-globin gene into zygotes and its subsequent expression in adult mice and their offspring. Proc Natl Acad Sci U S A. 1981;78:6376-6380.
42. Doetschman T, Gregg RG, Maeda N, et al. Targeted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature. 1987;330:576-578.
43. Thomas S, Clarke AR, Pow AM, Hopper ML, Melton DW. Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell. 1989;56:313-321.
44. Capecchi MR. Altering the genome by homologous recombination. Science. 1989;244:1288-1292.
45. Anderson WF. Prospects for human gene therapy. Science. 1984;226:401-409.
46. Parkman R, Gelfand EW, Rosen FS, Sanderson A, Hirschhorn R. Severe combined immunodeficiency and adenosine deaminase deficiency. N Engl J Med. 1975;292:714-719.
47. Kantoff PW, Gillio AP, McLachlin JR, et al. Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer. J Exp Med. 1987;166:219-234.
48. Miller AD, Buttimore C. Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol Cell Biol. 1986; 6:2895-2902.
49. Bender MA, Palmer TD, Gelinas RE, Miller AD. Evidence that the packaging singal of Moloney murine leukemia virus extends into the gag region. J Virol. 1987;61:1639-1646.
50. Armentano D, Yu SF, Kantoff PW, von Ruden T, Anderson WF, Gilboa E. Effect of internal viral sequences on the utility of retroviral vectors. J Virol. 1987;61:1647-1650.
51. Rosenberg SA, Aebersold P, Cornetta K, et al. Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumorinfiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990;323:601-603.
52. Ferrari G, Rossini S, Giavazzi R, et al. An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency. Science. 1991;251:1363-1366.
53. Ferrari G, Rossini S, Mobili N, et al. Transfer of the ADA gene into human ADA-deficient T lymphocytes reconstitutes specific immune functions. Blood. 1992;80:1120-1124.
54. Muul LM, Tuschong LM, Soenen SL, et al. Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial. Blood. 2003; 101:2563-2569.
55. Bordignon C, Notarangelo LD, Nobili N, et al. Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science. 1995;270:470-475.
56. Aiuti A, Vai S, Mortellaro A, et al. Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement. Nat Med. 2002;8:423-425.
57. Kohn DB, Weinberg KI, Nolta JA, et al. Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency. Nat Med. 1995;1:1017-1023.
58. + cells in ADA-deficient SCID neonates. Nat Med. 1998;4:775-780.
59. Brenner MK, Rill DR, Moen RC, et al. Genemarking to trace origin of relapse after autologous bone-marrow transplantation. Lancet. 1993;341:85-86.
60. Brenner MK, Rill DR, Holladay MS, et al. Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients. Lancet. 1993;342:1134-1137.
61. Rill DR, Santana VM, Roberts WM, et al. Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells. Blood. 1994;84:380-383.
62. Tey SK, Brenner MK. The continuing contribution of gene marking to cell and gene therapy. Mol Ther. 2007;15:666-676.
63. Sorrentino BP, Brandt SJ, Bodine D, et al. Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDRI. Science. 1992;257:99-103.
64. O'Shaughnessy JA, Cowan KH, Nienhuis AW, et al. Retroviral mediated transfer of the human multidrug resistance gene (MDR-1) into hematopoietic stem cells during autologous transplantation after intensive chemotherapy for metastatic breast cancer. Hum Gene Ther. 1994;5:891-911.
65. Abonour R, Williams DA, Einhorn L, et al. Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human longterm repopulating hematopoietic stem cells. Nat Med. 2000;6:624-626.
66. Orkin SH, Motulsky AG. Report and recommentations of the panel to assess the NIH investment in research on gene therapy. 1995. http://www.nih.gov/news/ panelrep.html. Accessed July 15, 2007.
67. Marechal V, Naffakh N, Danos O, Heard JM. Disappearance of lysosomal storage in spleen and liver of mucopolysaccharidosis VII mice after transplantation of genetically modified bone marrow cells. Blood. 1993;82:1358-1365.
68. Bunting KD, Sangster MY, Ihle JN, Sorrentino BP. Restoration of lymphocyte function in Janus kinase 3-deficient mice by retroviral-mediated gene transfer. Nat Med. 1998;4:58-64.
69. Bunting KD, Flynn KJ, Riberdy JM, Doherty PC, Sorrentino BP. Virus-specific immunity after gene therapy in a murine model of severe combined immunodeficiency. Proc Natl Acad Sci U S A. 1999;96:232-237.
70. Lo M, Bloom ML, Imada K, et al. Restoration of lymphoid populations in a murine model of X-linked severe combined immunodeficiency by a gene-therapy approach. Blood. 1999;94:3027-3036.
71. Soudais C, Shiho T, Sharara LI, et al. Stable and functional lymphoid reconstitution of common cytokine receptor gamma chain deficient mice by retroviral-mediated gene transfer. Blood. 2000; 95:3071-3077.
72. Otsu M, Anderson SM, Bodine DM, Puck JM, O'Shea JJ, Candotti F. Lymphoid development and function in X-linked severe combined immunodeficiency mice after stem cell gene therapy. Mol Ther. 2000;1:145-153.
73. Shepherd BE, Kiem HP, Lansdorp PM, et al. Hematopoietic stem cell behavior in non-human primates. Blood. 2007;110:1806-1813.
74. Larochelle A, Dunbar CE. Genetic manipulation of hematopoietic stem cells. Semin Hematol. 2004;41:257-271.
75. Trobridge G, Beard BC, Kiem HP. Hematopoietic stem cell transduction and amplification in large animal models. Hum Gene Ther. 2005;16:1355-1366.
76. Hanenberg H, Xiao XL, Dilloo D, Hashino K, Kato I, Williams DA. Colocalization of retrovirus and target cells on specific fibronectin fragmens increases genetic transduction of mammalian cells. Nat Med. 1996;2:876-882.
77. Miller AD, Garcia JV, von Suhr N, Lunch CM, Wilson C, Eiden MV. Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. J Virol. 1991;65:2220-2224.
78. Bauer TR Jr., Miller AD, Hickstein DD. Improved transfer of the leukocyte integrin CD18 subunit into hematopoietic cell lines by using retroviral vectors having a gibbon ape leukemia virus envelope. Blood. 1995;86:2379-2387.
79. Malech ML, Maples BP, Whiting-Theobald N, et al. Prolonged production of NADPH oxidasecorrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci U S A. 1997;94:12133-12138.
80. Cavazzana-Calvo M, Fischer A. Gene therapy for severe combined immunodeficiency: are we there yet? J Clin Invest. 2007;117:1456-1465.
81. Gaspar HB, Bjorkegren E, Parsley K, et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol Ther. 2006;14:505-513.
82. Hacein-Bey-Avina 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;302:415-419.
83. Thrasher AJ, Hacein-Bey-Abina S, Gaspar HB, et al. Failure of SCID-X1 gene therapy in older patients. Blood. 2005;105:4255-4257.
84. Chinen J, Davis J, De Ravin SS, et al. Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency. Blood. 2007;110:67-73.
85. Ott MG, Schmidt M, Schwarzwaelder K, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBPI. Nat Med. 2006;12:401-409.
86. Baum C, Dullmann J, Li Z, et al. Side effects of retroviral gene transfer into hematopoietic stem cells. Blood. 2003;101:2099-2114.
87. Nienhuis AW, Dunbar CE, Sorrentino BP. Genotoxicity of retroviral integration in hematopoietic cells. Mol Ther. 2006;13:1031-1049.
88. Baum C. Insertional mutagenesis in gene therapy and stem cell biology. Curr Opin Hematol. 2007; 14:337-342.
89. Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science. 2003;300:1749-1752.
90. Schroder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F. HIV-1 integration in the human genome favors active genes and local hotspots. Cell. 2002;110:521-529.
91. Calmels B, Ferguson C, Laukkanen Mo, et al. Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells. Blood. 2005;106:2530-2533.
92. Deichmann A, Hacein-Bey-Abina S, Schmidt M, et al. Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. J Clin Invest. 2007;117:225-232.
93. Schwarzwaelder K, Howe SJ, Schmidt M, et al. Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo. J Clin Invest. 2007;117:2241-2249.
94. Aiuti A, Cassani B, Andolfi G, et al. Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy. J Clin Invest. 2007;117:2233-2240.
95. Shou Y, Ma Z, Lu T, Sorrentino BP. Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy. Proc Natl Acad Sci U S A. 2006;103:11730-11735.
96. Seggewiss R, Pittaluga S, Adler Rl, et al. Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque. Blood. 2006;107:3865-3867.
97. Nienhuis AW. Assays to evaluate the genotoxicity of retroviral vectors. Mol Ther. 2006;14:459-460.
98. Gaszner M, Felsenfeld G. Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet. 2006;7:703-713.
99. Evans-Galea MV, Wielgosz MM, Hanawa H, Srivastava D, Nienhuis AW. Suppression of clonal dominance in cultured human lymphoid cells by addition of the cHS4 insulator to a lentiviral vector. Mol Ther. 2007;15:801-809.
100. Chang AH, Sadelain M. The genetic engineering of hematopoietic stem cells: the rise of lentiviral vectors, the conundrum of the LTR, and the promise of lineage-restricted vectors. Mol Ther. 2007;15:445-456.
101. Ryu BY, Evans-Galea MV, Gray JT, Bodine DM, Persons DA, Nienhuis AW. An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation. Blood. 2008;111:1866-1875.
102. Bonini C, Bondanza A, Perna SK, et al. The suicide gene therapy challenge: how to improve a successful gene therapy approach. Mol Ther. 2007;15:1248-1252.
103. Recchia A, Bonini C, Magnani Z, et al. Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells. Proc Natl Acad Sci U S A. 2006;103:1457-1462.
104. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science. 1992;10:238-241.
105. Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345:9-13.
106. Rossig C, Brenner MK. Genetic modification of T lymphocytes for adoptive immunotherapy. Mol Ther. 2004;10:5-18.
107. Tey SK, Bollard CM, Heslop HE. Adoptive T-cell transfer in cancer immunotherapy. Immunol Cell Biol. 2006;84:281-289.
108. Leen AM, Myers GD, Sili U, et al. Monoculturederived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med. 2006;12:1160-1166.
109. Baltimore D. Gene therapy. Intracellular immunization. Nature. 1988;335:395-396.
110. Freidman AD, Triezenberg SJ, McKnight SL. Expression of a truncated viral trans-activator selectively impedes lytic infection by its cognate virus. Nature. 1988;335:452-454.
111. Scherer L, Rossi JJ, Weinberg MS. Progress and prospects: RNA-based therapies for treatment of HIV infection. Gene Ther. 2007;14:1057-1064.
112. Levine BL, Humeau LM, Boyer J, et al. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci U S A. 2006;103:17372-17377.
113. Cohen J. Building an HIV-proof immune system. Science. 2007;317:612-614.
114. Anderson J, Li MJ, Palmer B, et al. Safety and efficacy of a lentiviral vector containing three anti-HIV genes-CCR5 ribozyme, tat-rev siRNA and TAR decoy-in SCID-hu mouse-derived T cells. Mol Ther. 2007;15:1182-1188.
115. Laheru DA, Pardoll DM, Jaffee EM. Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology. Mol Cancer Ther. 2005;4:1645-1652.
116. Hodi FS, Dranoff G. Combinatorial cancer immunotherapy. Adv Immunol. 2006;90:341-368.
117. Hege KM, Jooss K, Pardoll D. GM-CSF genemodified cancer cell immunotherapies: of mice and men. Int Rev Immunol. 2006;25:321-352.
118. Brentijens RJ, Sadelain M. Somatic cell engineering and the immunotherapy of leukemias and lymphomas. Adv Pharmacol. 2004;52:347-370.
119. Bollard CM, Gottschalk S, Leen AM, et al. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood. 2007;110:2838-2845.
120. Rousseau RF, Biagi E, Dutour A, et al. Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Blood. 2006; 107:1332-1341.
121. Brentjens RJ, Latouche JB, Santos E, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes costimulated by CD80 and interleukin-15. Nat Med. 2003;9:279-286.
122. Imai Ciwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemia cells. Blood. 2005;106:376-383.
123. Nathwani AC, McIntosh J, Davidoff AM. An update on gene therapy for hemophilia. Curr Hematol Rep. 2005;4:287-293.
124. Ponder KP. Gene therapy for hemophilia. Curr Opin Hematol. 2006;13:301-307.
125. Ide LM, Gangadharan B, Chiang KY, Doering CB, Spencer HT. Hematopoietic stem cell gene therapy for hemophilia A incorporating a porcine factor VIII transgene and nonmyeloablative conditioning regiments. Blood. 2007;110:2855-2863.
126. Chang AH, Stephan MT, Sadelain M. Stem cellderived erythroid cells mediated long-term systemic protein delivery. Nat Biotechnol. 2006;24:1017-1021.
127. Matsui H, Shibata M, Brown B, et al. Ex vivo gene therapy for hemophilia A that enhances safe delivery and sustained in vivo FVII expression from lentivirally engineered endothelial progenitors. Stem Cells. 2007;25:2660-2669.
128. Manno CS, Chew AJ, Hutchinson S, et al. AAVmediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood. 2003;101:2963-2972.
129. Nathwani AC, Davidoff A, Hanawa H, Zhou JF, Vanin EF, Nienhuis AW. Factors influencing in vivo transduction by recombinant adenoassociated viral vectors expressing the human factor IX cDNA. Blood. 2001;97:1258-1265.
130. Manno CS, Pierce GF, Arruda VR, et al. Successful transduction of liver in hemophilia by AAVFactor IX and limitations imposed by the host immune response. Nat Med. 2006;12:342-347.
131. Nathwani AC, Gray JT, Ng CY, et al. Selfcomplementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood. 2006;107:2653-2661.
132. Nathwani AC, Gray JT, McIntosh J, et al. Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood. 2007;15:1414-1421.
133. Donsante A, Miller DG, Li Y, et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science. 2007;317:477.
134. Mingozzi F, Maus MV, Hui DJ, et al. CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat Med. 2007;13:419-422.
135. + T cells are unable to eliminate AAV-transduced hepatocytes. Mol Ther. 2007;14:792-800.
136. 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;108:3321-3328.
137. Dzierzak EA, Papayannopoulou T, Mulligan RC. Lineage-specific expression of a human betaglobin gene in murine bone marrow transplant recipients reconstituted with retrovirustransduced stem cells. Nature. 1988;331:35-41.
138. Grosveld F, van Assendelft GB, Greaves DR, Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987;51:975-985.
139. Tuan D, London IM. Mapping of DNase I-hypersensitive sites in the upstream DNA of human embryonic epsilon-globin gene in K562 leukemia cells. Prac Natl Acad Sci U S A. 1984;81:2718-2722.
140. Leboulch P, Huang GM, Humphries RK, et al. Mutagenesis of retroviral vectors transducing human beta-globin gene and beta-globin locus control region derivatives results in stable transmission of an active transcriptional structure. EMBO J. 1994;13:3065-3076.
141. Sadelain M, Wang CH, Antoniou M, Grosveld F, Mulligan RC. Generation of a high-titer retroviral vector capable of expressing high levels of the human beta-globin gene. Proc Natl Acad Sci U S A. 1995;92:6728-6732.
142. May C, Rivella S, Callegarl J, et al. Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin. Nature. 2000;406:82-86.
143. May C, Rivella S, Chadburn A, Sadelain M. Successful treatment of murine β-thalassaemic intermedia by transfer of the human β-globin gene. Blood. 2002;99:1902-1908.
144. Hanawa H, Hargrove PW, Kepes S, Srivastava DK, Nienhuis AW, Persons DA. Extended β-globin locus control region elements promote consistent therapeutic expression of a β-globin lentiviral vector in murine β-thalassemia. Blood. 2004;104:2281-2290.
145. Pawliuk R, Westerman KA, Fabry ME, et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science. 2001;294:2368-2371.
146. Puthenveetil G, Scholes J, Carbonell D, et al. Successful correction of the human betathalassemia major phenotype using a lentiviral vector. Blood. 2004;104:3445-3453.
147. Rivella S, May C, Chadburn A, Riviere I, Sadelain M. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human β-globin gene transfer. Blood. 2003;101:2932-2939.
148. Persons DA, Allay ER, Sabatino DE, Kelly P, Bodine DM, Nienhuis AW. Functional requirements for phenotypic correction of murine betathalassemia: implications for human gene therapy. Blood. 2001;97:3275-3282.
149. Emery DW, Yannaki E, Tubb J, Stamatoyannopoulos G. A chromatin insulator protects retrovirus vectors from chromosomal position effects. Proc Natl Acad Sci U S A. 2000;97:9150-9155.
150. Arumugam PI, Scholes J, Perelman N, Xia P, Yee JK, Malik P. Improved human beta-globin expression from self-inactivating lentiviral vectors carrying the chicken hypersensitive site-4 (cHS4) insulator element. Mol Ther. 2007;15:1863-1871.
151. Xu K, Ma H, McCown TJ, Verma IM, Kafri T. Generation of a stable cell line producing high-titer self-inactivating lentiviral vectors. Mol Ther. 2001; 1:97-104.
152. Ikeda Y, Takeuchi Y, Martin F, Cosset FL, Mitrophanous K, Collins M. Continuous high-titer HIV-1 vector production. Nat Biotechnol. 2003;21:569-572.
153. Sands MS, Davidson BL. Gene therapy for lysosomal diseases. Mol Ther. 2006;13:839-849.
154. Retracing events [editorial]. Nat Biotech. 2007; 25:949.