Therapeutic globin gene delivery using lentiviral vectors

Current Opinion in Molecular Therapeutics

Volumn 4, Issue 5, 2002, Pages 505-514

  Rivella, Stefano ^a   Sadelain, Michel ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

thalassemia; Gene therapy; Globin gene regulation; Hematopoietic stem cell; Lentiviral vector; Sickle cell disease

Indexed keywords

5 AMINOLEVULINATE SYNTHASE; ALPHA GLOBULIN; ANKYRIN; BETA GLOBIN; CD34 ANTIGEN; CYTOTOXIC AGENT; DEOXYRIBONUCLEASE I; GAG PROTEIN; GREEN FLUORESCENT PROTEIN; HYDROXYUREA; IMMUNOGLOBULIN; LENTIVIRUS VECTOR; MESSENGER RNA; PLASMID VECTOR; RETROVIRUS VECTOR; REV PROTEIN; RNA; SPECTRIN; THROMBOSPONDIN; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR GATA 1; TRANSCRIPTION FACTOR NF E2; VIRUS PROTEIN; VIRUS RNA;

BETA THALASSEMIA; BONE MARROW CELL; DISEASE SEVERITY; DRUG EFFICACY; DRUG PACKAGING; DRUG SAFETY; ERYTHROID CELL; GENE CONTROL; GENE EXPRESSION; GENE THERAPY; GENE TRANSFER; GENETIC STABILITY; GENETIC TRANSCRIPTION; GENETIC TRANSDUCTION; GENETIC TRANSFECTION; HEMATOPOIETIC STEM CELL; HEMOGLOBINOPATHY; HEPATITIS VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; ONCOVIRINAE; PROMOTER REGION; REGULATOR GENE; REVIEW; SICKLE CELL ANEMIA; TISSUE SPECIFICITY; TRANSGENE; VIRAL GENE DELIVERY SYSTEM; VIRUS RECOMBINANT; VIRUS REPLICATION;

GENETIC VECTORS; GLOBINS; HUMANS; LENTIVIRUS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; LENTIVIRUS; MURINAE; ONCOVIRINAE; UNIDENTIFIED RETROVIRUS;

EID: 0036819745     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (153)

1. Weatherall DJ, Clegg JB: The Thalassemia Syndrome. Blackwell Scientific, Oxford, UK (1981).
2. Stamatoyannopoulos G, Perlmutter RM, Majerus PW, Varmus H: The Molecular Basis of Blood Diseases, 3rd Edition. WB Saunders, Philadelphia, PA, USA (2001).
3. Steinberg MH, Forget BG, Higgs DR, Nagel RL: Disorders of Hemoglobin: Genetics, Pathophysiology and Clinical Management. Cambridge University Press, Cambridge, UK (2001).
4. Weatherall DJ: Phenotype-genotype relationships in monogenic disease: Lessons from the thalassaemias. Nat Rev Genet (2001) 2:245-255.
5. Cooley TB, Lee P: A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr Soc (1925) 37:29.
6. Giardina PJ, Grady RW: Chelation therapy in β-thalassemia: An optimistic update. Semin Hematol (2001) 38:360-366.
7. Giardini C, Lucarelli G: Bone marrow transplantation in the treatment of thalassemia. Curr Opin Hematol (1994) 1:170-176.
8. Boulad F, Giardina P, Gillio A, Kernan N, Small T, Brochstein J, Van Syckle K, George D, Szabolcs P, O'Reilly RJ: Bone marrow transplantation for homozygous β-thalassemia. The Memorial Sloan-Kettering Cancer Center experience. Ann NY Acad Sci (1998) 850:498-502.
9. Lucarelli G, Clift RA, Galimberti M, Angelucci E, Giardini C, Baronciani D, Polchi P, Andreani M, Gaziev D, Erer B, Ciaroni A et al: Bone marrow transplantation in adult thalassemic patients. Blood (1999) 93:1164-1167.
10. Tisdale J, Sadelain M: Toward gene therapy for disorders of globin synthesis. Semin Hematol (2001) 38:382-392.
11. Pauling L, Itano HA, Singer SJ, Wells IC: Sickle cell anemia, a molecular disease. Science (1949) 110:543-546.
12. Swank RA, Stamatoyannopoulos G: Fetal gene reactivation. Curr Opin Genet Dev (1998) 8:366-370.
13. Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG: Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest (1984) 74:652-656.
14. Charache S, Dover GJ, Moore RD, Eckert S, Ballas SK, Koshy M, Milner PF, Orringer EP, Phillips G, Platt OS: Hydroxyurea: Effects on hemoglobin F production in patients with sickle cell anemia. Blood (1992) 79:2555-2565.
15. Atweh GF, Loukopoulos D: Pharmacological induction of fetal hemoglobin in sickle cell disease and β-thalassemia. Semin Hematol (2001) 38:367-373.
16. Luzzatto L, Goodfellow P: Sickle cell anaemia. A simple disease with no cure. Nature (1989) 337:17-18.
17. Vermylen C, Cornu G, Ferster A, Brichard B, Ninane J, Ferrant A, Zenebergh A, Maes P, Dhooge C, Benoit Y, Dresse MF et al: Haematopoietic stem cell transplantation for sickle cell anaemia: The first 50 patients transplanted in Belgium. Bone Marrow Transplant (1998) 22:1-6.
18. Sadelain M: Genetic treatment of the haemoglobinopathies: Recombinations and new combinations. Br J Haematol (1997) 98:247-253.
19. Dunbar CE: Gene transfer to hematopoietic stem cells: Implications for gene therapy of human disease. Annu Rev Med (1996) 47:11-20.
20. McInerney JM, Nemeth MJ, Lowrey CH: Erythropoiesis: Review article: Slow and steady wins the race? Progress in the development of vectors for gene therapy of β-thalassemia and sickle cell disease. Hematology (2000) 4:437-455.
21. Sadelain M: Globin gene transfer for the treatment of severe hemoglobinopathies: A paradigm for stem cell-based gene therapy. J Gene Med (2002) 4:113-121.
22. Rivella S, Sadelain M: Genetic treatment of severe hemoglobinopathies: The combat against transgene variegation and transgene silencing. Semin Hematol (1998) 35:112-125.
23. Persons DA, Nienhuis AW: Gene therapy for the hemoglobin disorders: Past, present, and future. Proc Natl Acad Sci USA (2000) 97:5022-5024
24. Ellis J, Pannell D: The β-globin locus control region versus gene therapy vectors: A struggle for expression. Clin Genet (2001) 59:17-24.
25. Leboulch P, Huang GM, Humphries RK, Oh YH, Eaves CJ, Tuan DY, London IM: Mutagenesis of retroviral vectors transducing human β-globin gene and β-globin locus control region derivatives results in stable transmission of an active transcriptional structure. EMBO J (1994) 13:3065-3076.
26. 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 β-globin gene. Proc Natl Acad Sci USA (1995) 92:6728-6732.
27. May C, Rivella S, Callegari J, Heller G, Gaensler KM, Luzzatto L, Sadelain M: Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin. Nature (2000) 406:82-86.
28. Higgs DR: Do LCRs open chromatin domains? Cell (1998) 95:299-302.
29. Bulger M, Groudine M: Looping versus linking: Toward a model for long-distance gene activation. Genes Dev (1999) 13:2465-2477.
30. Grosveld F: Activation by locus control regions? Curr Opin Genet Dev (1999) 9:152-157.
31. Engel JD, Tanimoto K: Looping, linking, and chromatin activity: New insights into β-globin locus regulation. Cell (2000) 100:499-502.
32. Bulger M, Sawado T, Schubeler D, Groudine M: ChIPs of the β-globin locus: Unraveling gene regulation within an active domain. Curr Opin Genet Dev (2002) 12:170-177.
33. de Krom M, van de Corput M, von Lindem M, Grosveld F, Strouboulis J: Stochastic patterns in globin gene expression are established prior to transcriptional activation and are clonally inherited. Mol Cell (2002) 9:1319-1326.
34. Levings PP, Bungert J: The human β-globin locus control region. Eur J Biochem (2002) 269:1589-1599.
35. Navas PA, Li Q, Peterson KR, Swank RA, Rohde A, Roy J, Stamatoyannopoulos G: Activation of the β-like globin genes in transgenic mice is dependent on the presence of the β-locus control region. Hum Mol Genet (2002) 11:893-903.
36. Forget BG: Molecular mechanisms of β-thalassemia. In: Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management Steinberg MH, Forget BG, Higgs DR, Nagel RL (Eds), Cambridge University Press, Cambridge, UK (2001):252-276.
37. Trudel M, Costantini F: A 3′ enhancer contributes to the stage-specific expression of the human β-globin gene. Genes Dev (1987) 1:954-961.
38. Trudel M, Magram J, Bruckner L, Costantini F: Upstream G γ-globin and downstream β-globin sequences required for stage-specific expression in transgenic mice. Mol Cell Biol (1987) 7:4024-4029.
39. Antoniou M, deBoer E, Habets G, Grosveld F: The human β-globin gene contains multiple regulatory regions: Identification of one promoter and two downstream enhancers. EMBO J (1988) 7:377-384.
40. Grosveld F, van Assendelft GB, Greaves DR, Kollias G: Position-independent, high-level expression of the human β-globin gene in transgenic mice. Cell (1987) 51:975-985.
41. Tuan DY, Solomon WB, London IM, Lee DP: An erythroid-specific, developmental-stage-independent enhancer far upstream of the human "β-like globin" genes. Proc Natl Acad Sci USA (1989) 86:2554-2558.
42. Talbot D, Grosveld F: The 5′HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites. EMBO J (1991) 10:1391-1398.
43. Fraser P, Pruzina S, Antoniou M, Grosveld F: Each hypersensitive site of the human β-globin locus control region confers a different developmental, pattern of expression on the globin genes. Genes Dev (1993) 7:106-113.
44. Miller JL, Walsh CE, Ney PA, Samulski RJ, Nienhuis AW: Single-copy transduction and expression of human γ-globin in K562 erythroleukemia cells using recombinant adeno-associated virus vectors: The effect of mutations in NF-E2 and GATA-1 binding motifs within the hypersensitivity site 2 enhancer. Blood (1993) 82:1900-1906.
45. Ney PA, Andrews NC, Jane SM, Safer B, Purucker ME, Weremowicz S, Morton CC, Goff SC, Orkin SH, Nienhuis AW: Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. Mol Cell Biol (1993) 13:5604-5612.
46. Ryan TM, Behringer RR, Marlin NC, Townes TM, Palmiter RD, Brinster RL: A single erythroid-specific DNase I super-hypersensitive site activates high levels of human β-globin gene expression in transgenic mice. Genes Dev (1989) 3:314-323.
47. Philipsen S, Talbot D, Fraser P, Grosveld F: The β-globin dominant control region: Hypersensitive site 2. EMBO J (1990) 9:2159-2167.
48. Talbot D, Philipsen S, Fraser P, Grosveld F: Detailed analysis of the site 3 region of the human β-globin dominant control region. EMBO J (1990) 9:2169-2177.
49. Liu D, Chang JC, Moi P, Liu W, Kan YW, Curtin PT: Dissection of the enhancer activity of β-globin 5′ DNase I-hypersensitive site 2 in transgenic mice. Proc Natl Acad Sci USA (1992) 89:3899-3903.
50. Talbot D, Collis P, Antoniou M, Vidal M, Grosveld F, Greaves DR: A dominant control region from the human β-globin locus conferring integration site-independent gene expression. Nature (1989) 338:352-355.
51. Pasceri P, Pannell D, Wu X, Ellis J: Full activity from human β-globin locus control region transgenes requires 5′HS1, distal β-globin promoter, and 3′ β-globin sequences. Blood (1998) 92:653-663.
52. Li Q, Zhang M, Duan Z, Stamatoyannopoulos G: Structural analysis and mapping of DNase I hypersensitivity of HS5 of the β-globin locus control region. Genomics (1999) 61:183-193.
53. Li Q, Stamatoyannopoulos G: Hypersensitive site 5 of the human β-locus control region functions as a chromatin insulator. Blood (1994) 84:1399-1401.
54. Li Q, Zhang M, Han H, Rohde A, Stamatoyannopoulos G: Evidence that DNase I hypersensitive site 5 of the human β-globin locus control region functions as a chromosomal insulator in transgenic mice. Nucleic Acids Res (2002) 30:2484-2491.
55. Molete JM, Petrykowska H, Bouhassira EE, Feng YQ, Miller W, Hardison RC: Sequences flanking hypersensitive sites of the β-globin locus control region are required for synergistic enhancement. Mol Cell Biol (2001) 21:2969-2980.
56. Bender MA, Roach JN, Halow J, Close J, Alami R, Bouhassira EE, Groudine M, Fiering SN: Targeted deletion of 5′HS1 and 5′HS4 of the β-globin locus control region reveals additive activity of the DNasel hypersensitive sites. Blood (2001) 98:2022-2027.
57. Forrester WC, Epner E, Driscoll MC, Enver T, Brice M, Papayannopoulou T, Groudine M: A deletion of the human β-globin locus activation region causes a major alteration in chromatin structure and replication across the entire β-globin locus. Genes Dev (1990) 4:1637-1649.
58. Reik A, Telling A, Zitnik G, Cimbora D, Epner E, Groudine M: The locus control region is necessary for gene expression in the human β-globin locus but not the maintenance of an open chromatin structure in erythroid cells. Mol Cell Biol (1998) 18:5992-6000.
59. Cone RD, Weber-Benarous A, Baorto D, Mulligan RC: Regulated expression of a complete human β-globin gene encoded by a transmissible retrovirus vector. Mol Cell Biol (1987) 7:887-897.
60. Karlsson S, Papayannopoulou T, Schweiger SG, Stamatoyannopoulos G, Nienhuis AW: Retroviral-mediated transfer of genomic globin genes leads to regulated production of RNA and protein. Proc Natl Acad Sci USA (1987) 84:2411-2415.
61. Dzierzak EA, Papayannopoulou T, Mulligan RC: Lineage-specific expression of a human β-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells. Nature (1988) 331:35-41.
62. Bender MA, Gelinas RE, Miller AD: A majority of mice show long-term expression of a human β-globin gene after retrovirus transfer into hematopoietic stem cells. Mol Cell Biol (1989) 9:1426-1434.
63. Bodine DM, Karlsson S, Nienhuis AW: Combination of interleukins 3 and 6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells. Proc Natl Acad Sci USA (1989) 86:8897-8901.
64. Plavec I, Papayannopoulou T, Maury C, Meyer F: A human β-globin gene fused to the human β-globin locus control region is expressed at high levels in erythroid cells of mice engrafted with retrovirus-transduced hematopoietic stem cells. Blood (1993) 81:1384-1392.
65. Chang JC, Liu D, Kan YW: A 36-base-pair core sequence of locus control region enhances retrovirally transferred human β-globin gene expression. Proc Natl Acad Sci USA (1992) 89:3107-3110.
66. Novak U, Harris EA, Forrester W, Groudine M, Gelinas R: High-level β-globin expression after retroviral transfer of locus activation region-containing human β-globin gene derivatives into murine erythroleukemia cells. Proc Natl Acad Sci USA (1990) 87:3386-3390.
67. Ellis J, Pasceri P, Tan-Un KC, Wu X, Harper A, Fraser P, Grosveld F: Evaluation of β-globin gene therapy constructs in single copy transgenic mice. Nucleic Acids Res (1997) 25:1296-1302.
68. Einerhand MP, Antoniou M, Zolotukhin S, Muzyczka N, Berns KI, Grosveld F, Valerio D: Regulated high-level human β-globin gene expression in erythroid cells following recombinant adeno-associated virus-mediated gene transfer. Gene Ther (1995) 2:336-343.
69. Ponnazhagan S, Yoder MC, Srivastava A: Adeno-associated virus type 2-mediated transduction of murine hematopoietic cells with long-term repopulating ability and sustained expression of a human globin gene in vivo. J Virol (1997) 71:3098-3104.
70. Bertran J, Yang Y, Hargrove P, Vanin EF, Nienhuis AW: Targeted integration of a recombinant globin gene adeno-associated viral vector into human chromosome 19. Ann NY Acad Sci (1998) 850:163-177.
71. Chow CM, Athanassiadou A, Raguz S, Psiouri L, Harland L, Malik M, Aitken MA, Grosveld F, Antoniou M: LCR-mediated, long-term tissue-specific gene expression within replicating episomal plasmid and cosmid vectors. Gene Ther (2002) 9:327-336.
72. Ren S, Wong BY, Li J, Luo XN, Wong PM, Atweh GF: Production of genetically stable high-titer retroviral vectors that carry a human γ-globin gene under the control of the α-globin locus control region. Blood (1996) 87:2518-2524.
73. Emery DW, Morrish F, Li Q, Stamatoyannopoulos G: Analysis of γ-globin expression cassettes in retrovirus vectors. Hum Gene Ther (1999) 10:877-888.
74. Lung HY, Meeus IS, Weinberg RS, Atweh GF: In vivo silencing of the human γ-globin gene in murine erythroid cells following retroviral transduction. Blood Cells Mol Dis (2000) 26:613-619.
75. Sabatino DE, Wong C, Cline AP, Pyle L, Garrett LJ, Gallagher PG, Bodine DM: A minimal ankyrin promoter linked to a human γ-globin gene demonstrates erythroid specific copy number dependent expression with minimal position or enhancer dependence in transgenic mice. J Biol Chem (2000) 275:28549-28554.
76. Sabatino DE, Seidel NE, Aviles-Mendoza GJ, Cline AP, Anderson SM, Gallagher PG, Bodine DM: Long-term expression of γ-globin mRNA in mouse erythrocytes from retrovirus vectors containing the human γ-globin gene fused to the ankyrin-1 promoter. Proc Natl Acad Sci USA (2000) 97:13294-13299.
77. Rivella S, Callegari JA, May C, Tan CW, Sadelain M: The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites. J Virol (2000) 74:4679-4687.
78. Yannaki E, Tubb J, Aker M, Stamatoyannopoulos G, Emery DW: Topological constraints governing the use of the chicken HS4 chromatin insulator in oncoretrovirus vectors. Mol Ther (2002) 5:589-598.
79. Coffin JM, Hughes SH, Varmus HE: Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA (1997).
80. Cullen BR: Retroviruses as model systems for the study of nuclear RNA export pathways. Virology (1998) 249:203-210.
81. Pollard VW, Malim MH: The HIV-1 Rev protein. Annu Rev Microbiol (1998) 52:491-532.
82. Felber BK, Hadzopoulou-Cladaras M, Cladaras C, Copeland T, Pavlakis GN: Rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci USA (1989) 86:1495-1499.
83. Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR: The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature (1989) 338:254-257.
84. Fischer U, Huber J, Boelens WC, Mattaj IW, Luhrmann R: The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell (1995) 82:475-483.
85. Wen W, Meinkoth JL, Tsien RY, Taylor SS: Identification of a signal for rapid export of proteins from the nucleus. Cell (1995) 82:463-473.
86. Fornerod M, Ohno M, Yoshida M, Mattaj IW: CRM1 is an export receptor for leucine-rich nuclear export signals. Cell (1997) 90:1051-1060.
87. Yi R, Bogerd HP, Cullen BR: Recruitment of the Crm1 nuclear export factor is sufficient to induce cytoplasmic expression of incompletely spliced human immunodeficiency virus mRNAs. J Virol (2002) 76:2036-2042.
88. Yi R, Bogerd HP, Wiegand HL, Cullen BR: Both ran and importins have the ability to function as nuclear mRNA export factors. RNA (2002) 8:180-187.
89. Bohnlein E, Berger J, Hauber J: Functional mapping of the human immunodeficiency virus type 1 Rev RNA binding domain: New insights into the domain structure of Rev and Rex. J Virol (1991) 65:7051-7055.
90. Vigna E, Naldini L: Lentiviral vectors: Excellent tools for experimental gene transfer and promising candidates for gene therapy. J Gene Med (2000) 2:308-316.
91. Salmon P, Trono D: Lentiviral vectors for the gene therapy of lympho-hematological disorders. Curr Top Microbiol Immunol (2002) 261:211-227.
92. Lewis PF, Emerman M: Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol (1994) 68:510-516.
93. Goff SP: Intracellular trafficking of retroviral genomes during the early phase of infection: Viral exploitation of cellular pathways. J Gene Med (2001) 3:517-528.
94. Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM: Development of a self-inactivating lentivirus vector. J Virol (1998) 72:8150-8157.
95. Miyoshi H, Smith KA, Mosier DE, Verma IM, Torbett BE: Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science (1999) 283:682-686.
96. Guenechea G, Gan OI, Inamitsu T, Dorrell C, Pereira DS, Kelly M, Naldini L, Dick JE: Transduction of human CD34+ CD38- bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors. Mol Ther (2000) 1:566-573.
97. Dyall J, Latouche JB, Schnell S, Sadelain M: Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes. Blood (2001) 97:114-121.
98. Follenzi A, Sabatino G, Lombardo A, Boccaccio C, Naldini L: Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum Gene Ther (2002) 13:243-260.
99. Mangeot PE, Duperrier K, Negre D, Boson B, Rigal D, Cosset FL, Darlix JL: High levels of transduction of human dendritic cells with optimized SIV vectors. Mol Ther (2002) 5:283-290.
100. Sutton RE, Reitsma MJ, Uchida N, Brown PO: Transduction of human progenitor hematopoietic stem cells by human immunodeficiency virus type 1-based vectors is cell cycle dependent. J Virol (1999) 73:3649-3660.
101. Sadelain M, Frassoni F, Riviere I: Issues in the manufacture and transplantation of genetically modified hematopoietic stem cells. Curr Opin Hematol (2000) 7:364-377.
102. Kumar M, Keller B, Makalou N, Sutton RE: Systematic determination of the packaging limit of lentiviral vectors. Hum Gene Ther (2001) 12:1893-1905.
103. Sadelain M, Riviere I: The advent of lentiviral vectors: Prospects for cancer therapy. In: Gene Therapy for Cancer. Lattime EC, Gerson SL (Eds), Academic Press, San Diego, CA, USA (2002):109-124.
104. Miller AD: Development and applications of retroviral vectors. In: Retroviruses. Coffin JM, Hughes SH, Varmus HE (Eds), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA (1997).
105. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D: Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol (1997) 15:871-875.
106. Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK: Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: Concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA (1993) 90:8033-8037.
107. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L: A third-generation lentivirus vector with a conditional packaging system. J Virol (1998) 72:8463-8471.
108. Wu X, Wakefield JK, Liu H, Xiao H, Kralovics R, Prchal JT, Kappes JC: Development of a novel trans-lentiviral vector that affords predictable safety. Mol Ther (2000) 2:47-55.
109. Bartz SR, Rogel ME, Emerman M: Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control. J Virol (1996) 70:2324-2331.
110. Li CJ, Friedman DJ, Wang C, Metelev V, Pardee AB: Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein. Science (1995) 268:429-431.
111. Miyazaki Y, Takamatsu T, Nosaka T, Fujita S, Martin TE, Hatanaka M: The cytotoxicity of human immunodeficiency virus type 1 Rev: Implications for its interaction with the nucleolar protein B23. Exp Cell Res (1995) 219:93-101.
112. Konvalinka J, Litterst MA, Welker R, Kottler H, Rippmann F, Heuser AM, Krausslich HG: An active-site mutation in the human immunodeficiency virus type 1 proteinase (PR) causes reduced PR activity and loss of PR-mediated cytotoxicity without apparent effect on virus maturation and infectivity. J Virol (1995) 69:7180-7186.
113. Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H: Transcriptional activation by tetracyclines in mammalian cells. Science (1995) 268:1766-1769.
114. Carroll R, Lin JT, Dacquel EJ, Mosca JD, Burke DS, St Louis DC: A human immunodeficiency virus type 1 (HIV-1)-based retroviral vector system utilizing stable HIV-1 packaging cell lines. J Virol (1994) 68:6047-6051.
115. Yu H, Rabson AB, Kaul M, Ron Y, Dougherty JP: Inducible human immunodeficiency virus type 1 packaging cell lines. J Virol (1996) 70:4530-4537.
116. Srinivasakumar N, Chazal N, Helga-Maria C, Prasad S, Hammarskjold ML, Rekosh D: The effect of viral regulatory protein expression on gene delivery by human immunodeficiency virus type 1 vectors produced in stable packaging cell lines. J Virol (1997) 71:5841-5848.
117. Kaul M, Yu H, Ron Y, Dougherty JP: Regulated lentiviral packaging cell line devoid of most viral cis-acting sequences. Virology (1998) 249:167-174.
118. Kafri T, van Praag H, Ouyang L, Gage FH, Verma IM: A packaging cell line for lentivirus vectors. J Virol (1999) 73:576-584.
119. Kafri T, van Praag H, Gage FH, Verma IM: Lentiviral vectors: Regulated gene expression. Mol Ther (2000) 1:516-521.
120. Klages N, Zufferey R, Trono D: A stable system for the high-titer production of multiply attenuated lentiviral vectors. Mol Ther (2000) 2:170-176.
121. Farson D, Witt R, McGuinness R, Dull T, Kelly M, Song J, Radeke R, Bukovsky A, Consiglio A, Naldini L: A new-generation stable inducible packaging cell line for lentiviral vectors. Hum Gene Ther (2001) 12:981-997.
122. May C, Rivella S, Chadburn A, Sadelain M: Successful treatment of murine β-thalassemia intermedia by transfer of the human β-globin gene. Blood (2002) 99:1902-1908.
123. Pawliuk R, Westerman KA, Fabry ME, Payen E, Tighe R, Bouhassira EE, Acharya SA, Ellis J, London IM, Eaves CJ, Humphries RK et al: Correction of sickle cell disease in transgenic mouse models by gene therapy. Science (2001) 294:2368-2371.
124. Nagel RL, Bookchin RM, Johnson J, Labie D, Wajcman H, Isaac-Sodeye WA, Honig GR, Schiliro G, Crookston JH, Matsutomo K: Structural bases of the inhibitory effects of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S. Proc Natl Acad Sci USA (1979) 76:670-672.
125. Paszty C, Brion CM, Manci E, Witkowska HE, Stevens ME, Mohandas N, Rubin EM: Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. Science (1997) 278:876-878.
126. Trudel M, Saadane N, Garel MC, Bardakdjian-Michau J, Blouquit Y, Guerquin-Kern JL, Rouyer-Fessard P, Vidaud D, Pachnis A, Romeo PH: Towards a transgenic mouse model of sickle cell disease: Hemoglobin SAD. EMBO J (1991) 10:3157-3165.
127. Paszty C: Transgenic and gene knock-out mouse models of sickle cell anemia and the thalassemias. Curr Opin Hematol (1997) 4:88-93.
128. Huang ZM, Yen TS: Role of the hepatitis B virus posttranscriptional regulatory element in export of intronless transcripts. Mol Cell Biol (1995) 15:3864-3869.
129. Zufferey R, Donello JE, Trono D, Hope TJ: Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J Virol (1999) 73:2886-2892.
130. Burgess-Beusse B, Farrell C, Gaszner M, Litt M, Mutskov V, Recillas-Targa F, Simpson M, West A, Felsenfeld G: The insulation of genes from external enhancers and silencing chromatin. Proc Natl Acad Sci USA (2002): in press.
131. Farrell CM, West AG, Felsenfeld G: Conserved CTCF insulator elements flank the mouse and human β-globin loci. Mol Cell Biol (2002) 22:3820-3831.
132. Mutskov VJ, Farrell CM, Wade PA, Wolffe AP, Felsenfeld G: The barrier function of an insulator couples high histone acetylation levels with specific protection of promoter DNA from methylation. Genes Dev (2002) 16:1540-1554.
133. Zhang Q, Rombel I, Reddy GN, Gang JB, Shen CK: Functional roles of in vivo footprinted DNA motifs within an α-globin enhancer. Erythroid lineage and developmental stage specificities. J Biol Chem (1995) 270:8501-8505.
134. Grande A, Piovani B, Aiuti A, Ottolenghi S, Mavilio F, Ferrari G: Transcriptional targeting of retroviral vectors to the erythroblastic progeny of transduced hematopoietic stem cells. Blood (1999) 93:3276-3285.
135. Surinya KH, Cox TC, May BK: Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene. J Biol Chem (1998) 273:16798-16809.
136. Aγ- globin promoter prevents silencing of a linked human β-globin gene in transgenic mice. Mol Cell Biol (1998) 18:6634-6640.
137. Gallagher PG, Sabatino DE, Romana M, Cline AP, Garrett LJ, Bodine DM, Forget BG: A human β-spectrin gene promoter directs high level expression in erythroid but not muscle or neural cells. J Biol Chem (1999) 274:6062-6073.
138. Sabath DE, Koehler KM, Yang WQ, Patton K, Stamatoyannopoulos G: Identification of a major positive regulatory element located 5′ to the human ζ-globlin gene. Blood (1995) 85:2587-2597.
139. Huang BL, Fan-Chiang IR, Wen SC, Koo HC, Kao WY, Gavva NR, Shen CK: Derepression of human embryonic ζ-globin promoter by a locus-control region sequence. Proc Natl Acad Sci USA (1998) 95:14669-14674.
140. Takekoshi KJ, Oh YH, Westerman KW, London IM, Leboulch P: Retroviral transfer of a human β-globin/δ-globin hybrid gene linked to β locus control region hypersensitive site 2 aimed at the gene therapy of sickle cell disease. Proc Natl Acad Sci USA (1995) 92:3014-3018.
141. Moreau-Gaudry F, Xia P, Jiang G, Perelman NP, Bauer G, Ellis J, Surinya KH, Mavilio F, Shen CK, Malik P: High-level erythroid-specific gene expression in primary human and murine hematopoietic cells with self-inactivating lentiviral vectors. Blood (2001) 98:2664-2672.
142. Evans T, Felsenfeld G: The erythroid-specific transcription factor Eryf1: A new finger protein. Cell (1989) 58:877-885.
143. Tsai SF, Martin DI, Zon LI, D'Andrea AD, Wong GG, Orkin SH: Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature (1989) 339:446-451.
144. Nicolis S, Bertini C, Ronchi A, Crotta S, Lanfranco L, Moroni E, Giglioni B, Ottolenghi S: An erythroid specific enhancer upstream to the gene encoding the cell-type specific transcription factor GATA-1. Nucleic Acids Res (1991) 19:5285-5291.
145. Tsai SF, Strauss E, Orkin SH: Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev (1991) 5:919-931.
146. Ruggieri L, Aiuti A, Salomoni M, Zappone E, Ferrari G, Bordignon C: Cell-surface marking of CD34+-restricted phenotypes of human hematopoietic progenitor cells by retrovirus-mediated gene transfer. Hum Gene Ther (1997) 8:1611-1623.
147. Lotti F, Menguzzato E, Rossi C, Naldini L, Ailles L, Mavilio F, Ferrari G: Transcriptional targeting of lentiviral vectors by long terminal repeat enhancer replacement. J Virol (2002) 76:3996-4007.
148. Cornetta K, Smith FO: Regulatory issues for clinical gene therapy trials. Hum Gene Ther (2002) 13:1143-1149.
149. Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L: Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet (2000) 25:217-222.
150. Sirven A, Pflumio F, Zennou V, Titeux M, Vainchenker W, Coulombel L, Dubart-Kupperschmitt A, Charneau P: The human immunodeficiency Virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells. Blood (2000) 96:4103-4110.
151. Li Z, Dullmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J, Forster M, Stocking C, Wahlers A, Frank O, Ostertag W et al: Murine leukemia induced by retroviral gene marking. Science (2002) 296:497.
152. Stocking C, Bergholz U, Friel J, Klingler K, Wegener T, Starke C, Kitamura T, Miyajima A, Ostertag W: Distinct classes of factor-independent mutants can be isolated after retroviral mutagenesis of a human myeloid stem cell line. Growth Factors (1993) 8:197-209.
153. Sadelain M, Riviere I: Sturm und Drang over suicidal lymphocytes. Mol Ther (2002) 5:655-657.