Reducing the genotoxic potential of retroviral vectors

Methods in Molecular Biology

Volumn 434, Issue , 2008, Pages 183-203

  Ramezani, Ali ^a   Hawley, Teresa S ^a   Hawley, Robert G ^a  

^a GEORGE WASHINGTON UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Enhancer blocking sequences; Gammaretroviral vectors; Genotoxicity; Insertional mutagenesis; Lentiviral vectors; Post transcriptional regulatory elements; RNA end processing; Self inactivating vectors

Indexed keywords

LENTIVIRUS;

EID: 84934443000     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-60327-248-3_12     Document Type: Article

References (100)

1. Stewart, A. K., Dube, I. D., and Hawley, R. G. (1999) Gene marking and the biology of hematopoietic cell transfer in human clinical trials, in Blood Cell Biochemistry 8, Hematopoiesis and Gene Therapy (Fairbairn, L. J. and Testa, N., eds.), Kluwer Academic/Plenum Publishers, NY, pp. 243-268.
2. Kohn, D. B., Sadelain, M., Dunbar, C., Bodine, D., Kiem, H. P., Candotti, F. et al. (2003). American Society of Gene Therapy (ASGT) ad hoc subcommittee on retroviral-mediated gene transfer to hematopoietic stem cells. Mol. Ther. 8, 180-187.
3. Kiem, H. P., Sellers, S., Thomasson, B., Morris, J. C., Tisdale, J. F., Horn, P. A. et al. (2004). Long-term clinical and molecular follow-up of large animals receiving retrovirally transduced stem and progenitor cells: no progression to clonal hematopoiesis or leukemia. Mol. Ther. 9, 389-395.
4. Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P. et al. (2003). LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302, 415-419.
5. von Kalle, C., Fehse, B., Layh-Schmitt, G., Schmidt, M., Kelly, P., and Baum, C. (2004). Stem cell clonality and genotoxicity in hematopoietic cells: gene activation side effects should be avoidable. Semin. Hematol. 41, 303-318.
6. Baum, C., Kustikova, O., Modlich, U., Li, Z., and Fehse, B. (2006). Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum. Gene Ther. 17, 253-263.
7. Nienhuis, A. W., Dunbar, C. E., and Sorrentino, B. P. (2006). Genotoxicity of retroviral integration in hematopoietic cells. Mol. Ther. 13, 1031-1049.
8. Li, Z., Dullmann, J., Schiedlmeier, B., Schmidt, M., von Kalle, C., Meyer, J. et al. (2002). Murine leukemia induced by retroviral gene marking. Science 296, 497.
9. Kustikova, O., Fehse, B., Modlich, U., Yang, M., Dullmann, J., Kamino, K. et al. (2005). Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. Science 308, 1171-1174.
10. Modlich, U., Kustikova, O. S., Schmidt, M., Rudolph, C., Meyer, J., Li, Z. et al. (2005). Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. Blood 105, 4235-4246.
11. Du, Y., Spence, S. E., Jenkins, N. A., and Copeland, N. G. (2005). Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis. Blood 106, 2498-2505.
12. 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.
13. Calmeis, B., Ferguson, C., Laukkanen, M. O., Adler, R., Faulhaber, M., Kim, H. J. et al. (2005). Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells. Blood 106, 2530-2533.
14. Du, Y., Jenkins, N. A., and Copeland, N. G. (2005). Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells. Blood 106, 3932-3939.
15. Ott, M. G., 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.
16. Seggewiss, R., Pittaluga, S., Adler, R. L., Guenaga, F. J., Ferguson, C., Pilz, I. H. et al. (2006). Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque. Blood 107, 3865-3867.
17. Wu, X., Li, Y., Crise, B., and Burgess, S. M. (2003). Transcription start regions in the human genome are favored targets for MLV integration. Science 300, 1749-1751.
18. Bushman, F., Lewinski, M., Ciuffi, A., Barr, S., Leipzig, J., Hannenhalli, S. et al. (2005). Genome-wide analysis of retroviral DNA integration. Nat. Rev. Microbiol. 3, 848-858.
19. van Lohuizen, M. and Berns, A. (1990). Tumorigenesis by slow-transforming retroviruses-an update. Biochim. Biophys. Acta 1032, 213-235.
20. Askew, D. S., Bartholomew, C., and Ihle, J. N. (1993). Insertional mutagenesis and the transformation of hematopoietic stem cells. Hematol. Path. 1, 1-22.
21. Akagi, K., Suzuki, T., Stephens, R. M., Jenkins, N. A., and Copeland, N. G. (2004). RTCGD: retroviral tagged cancer gene database. Nucleic Acids Res. 32, 523-527.
22. Donahue, R. E., Kessler, S. W., Bodine, D., McDonagh, K., Dunbar, C., Goodman, S. et al. (1992). Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. J. Exp. Med. 176, 1125-1135.
23. Rangarajan, A., Hong, S. J., Gifford, A., and Weinberg, R. A. (2004). Speciesand cell type-specific requirements for cellular transformation. Cancer Cell 6, 171-183.
24. Armstrong, S. A. and Look, A. T. (2005). Molecular genetics of acute lymphoblastic leukemia. J. Clin. Oncol. 23, 6306-6315.
25. Lemischka, I. R., Raulet, D. H., and Mulligan, R. C. (1986). Developmental potential and dynamic behavior of hematopoietic stem cells. Cell 45, 917-27.
26. v mice. Proc. Natl. Acad. Sci. U. S. A. 86, 4564-4568.
27. Capel, B., Hawley, R. G., and Mintz, B. (1990). Long- and short-lived murine hematopoietic stem cell clones individually identified with retroviral integration markers. Blood 75, 2267-2270.
28. Mucenski, M. L., Taylor, B. A., Ihle, J. N., Hartley, J. W., Morse III, H. C., Jenkins, N. A. et al. (1988). Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors. Mol. Cell. Biol. 8, 301-308.
29. Hawley, R. G., Fong, A. Z. C., Ngan, B. Y., de Lanux, V. M., Clark, S. C., and Hawley, T. S. (1993). Progenitor cell hyperplasia with rare development of myeloid leukemia in interleukin 11 bone marrow chimeras. J. Exp. Med. 178, 1175-1188.
30. Hawley, T. S., Fong, A. Z. C., Griesser, H., Lyman, S. D., and Hawley, R. G. (1998). Leukemic predisposition of mice transplanted with gene-modified hematopoietic precursors expressing flt3 ligand. Blood 92, 2003-2011.
31. Dave, U. P., Jenkins, N. A., and Copeland, N. G. (2004). Gene therapy insertional mutagenesis insights. Science 303, 333.
32. Sternberg, D. W. and Gilliland, D. G. (2004). The role of signal transducer and activator of transcription factors in leukemogenesis. J. Clin. Oncol. 22, 361-371.
33. Song, W. J., Sullivan, M. G., Legare, R. D., Hutchings, S., Tan, X., Kufrin, D. et al. (1999). Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat. Genet. 23, 166-175.
34. Yan, H., Dobbie, Z., Gruber, S. B., Markowitz, S., Romans, K., Giardiello, F. M. et al. (2002). Small changes in expression affect predisposition to tumorigenesis. Nat. Genet. 30, 25-26.
35. Woods, N. B., Muessig, A., Schmidt, M., Flygare, J., Olsson, K., Salmon, P. et al. (2003). Lentiviral vector transduction of NOD/SCID repopulating cells results in multiple vector integrations per transduced cell: risk of insertional mutagenesis. Blood 101, 1284-1289.
36. Payne, S. R. and Kemp, C. J. (2005). Tumor suppressor genetics. Carcinogenesis 26, 2031-2045.
37. Themis, M., Waddington, S. N., Schmidt, M., von, K. C., Wang, Y., Al-Allaf, F. et al. (2005). Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice. Mol. Ther. 12, 763-771.
38. Hawley, R. G. (2001). Progress toward vector design for hematopoietic stem cell gene therapy. Curr. Gene Ther. 1, 1-17.
39. Baum, C., Schambach, A., Bohne, J., and Galla, M. (2006). Retrovirus vectors: toward the plentivirus? Mol. Ther. 13, 1050-1063.
40. Yu, S. F., von Rüden, T., Kantoff, P. W., Garber, C., Seiberg, M., Rüther, U. et al. (1986). Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc. Natl. Acad. Sci. U. S. A. 83, 3194-3198.
41. Hawley, R. G., Covarrubias, L., Hawley, T., and Mintz, B. (1987). Handicapped retroviral vectors efficiently transduce foreign genes into hematopoietic stem cells. Proc. Natl. Acad. Sci. U. S. A. 84, 2406-2410.
42. Miyoshi, H., Blomer, U., Takahashi, M., Gage, F. H., and Verma, I. M. (1998). Development of a self-inactivating lentivirus vector. J. Virol. 72, 8150-8157.
43. Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L. et al. (1998). Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol. 72, 9873-9880.
44. Kraunus, J., Schaumann, D. H., Meyer, J., Modlich, U., Fehse, B., Brandenburg, G. et al. (2004). Self-inactivating retroviral vectors with improved RNA processing. Gene Ther. 11, 1568-1578.
45. Ramezani, A., Hawley, T. S., and Hawley, R. G. (2006). Stable gammaretroviral vector expression during embryonic stem cell-derived in vitro hematopoietic development. Mol. Ther. 14, 245-254.
46. Schambach, A., Mueller, D., Galla, M., Verstegen, M. M., Wagemaker, G., Loew, R. et al. (2006). Overcoming promoter competition in packaging cells improves production of self-inactivating retroviral vectors. Gene Ther. 13, 1524-1533.
47. Felsenfeld, G., Burgess-Beusse, B., Farrell, C., Gaszner, M., Ghirlando, R., Huang, S. et al. (2004). Chromatin boundaries and chromatin domains. Cold Spring Harb. Symp. Quant. Biol. 69, 245-250.
48. Ellis, J. (2005). Silencing and variegation of gammaretrovirus and lentivirus vectors. Hum. Gene Ther. 16, 1246.
49. Emery, D. W., Yannaki, E., Tubb, J., and Stamatoyannopoulos, G. (2000). A chromatin insulator protects retrovirus vectors from chromosomal position effects. Proc. Natl. Acad. Sci. U. S. A. 97, 9150-9155.
50. Rivella, S., Callegari, J. A., May, C., Tan, C. W., and Sadelain, M. (2000). The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites. J. Virol. 74, 4679-4687.
51. Ma, Y., Ramezani, A., Lewis, R., Hawley, R. G., and Thomson, J. A. (2003). High-level sustained transgene expression in human embryonic stem cells using lentiviral vectors. Stem Cells 21, 111-117.
52. Ramezani, A., Hawley, T. S., and Hawley, R. G. (2003). Performance- and safety-enhanced lentiviral vectors containing the human interferon-β scaffold attachment region and the chicken β-globin insulator. Blood 101, 4717-4724.
53. Li, C and Emery, D. W. (2006). The cHS4 chromatin insulator blocks epigenetic interactions between integrated vectors and the surrounding genome. Mol. Ther. 13 (Suppl. 1), S405.
54. Evans-Galea, M. V., Wielgosz, M. M., Hanawa, H., and Nienhuis, A. W. (2006). Suppression of clonal dominance in cultured human lymphoid cells by addition of the 5′cHS4 insulator to a lentiviral vector. Mol. Ther. 13 (Suppl. 1), S405-S406.
55. Hantzopoulos, P. A., Sullenger, B. A., Ungers, G., and Gilboa, E. (1989). Improved gene expression upon transfer of the adenosine deaminase minigene outside the transcriptional unit of a retroviral vector. Proc. Natl. Acad. Sci. U. S. A. 86, 3519-3523.
56. Wiznerowicz, M., Fong, A. Z. C., Mackiewicz, A., and Hawley, R. G. (1997). Double-copy bicistronic retroviral vector platform for gene therapy and tissue engineering: application to melanoma vaccine development. Gene Ther. 4, 1061-1068.
57. Chung, J. H., Whiteley, M., and Felsenfeld, G. (1993). A 5′ element of the chicken β-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74, 505-514.
58. Chung, J. H., Bell, A. C., and Felsenfeld, G. (1997). Characterization of the chicken β-globin insulator. Proc. Natl. Acad. Sci. U. S. A. 94, 575-580.
59. Recillas-Targa, F., Pikaart, M. J., Burgess-Beusse, B., Bell, A. C., Litt, M. D., West, A. G. et al. (2002). Position-effect protection and enhancer blocking by the chicken β-globin insulator are separable activities. Proc. Natl. Acad. Sci. U. S. A. 99, 6883-6888.
60. Yao, S., Osbome, C. S., Bharadwaj, R. R., Pasceri, P., Sukonnik, T., Pannell, D. et al. (2003). Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Res. 31, 5317-5323.
61. Bell, A. C., West, A. G., and Felsenfeld, G. (1999). The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98, 387-396.
62. Guild, B. C., Finer, M. H., Housman, D. E., and Mulligan, R. C. (1988). Development of retrovirus vectors useful for expressing genes in cultured murine embryonal cells and hematopoietic cells in vivo. J. Virol. 62, 3795-3801.
63. De, P. M., Montini, E., de Sio, F. R., Benedicenti, F., Gentile, A., Medico, E. et al. (2005). Promoter trapping reveals significant differences in integration site selection between MLV and HIV vectors in primary hematopoietic cells. Blood 105, 2307-2315.
64. Logan, A. C., Haas, D. L., Kafri, T., and Kohn, D. B. (2004). Integrated self-inactivating lentiviral vectors produce full-length genomic transcripts competent for encapsidation and integration. J. Virol. 78, 8421-8436.
65. Hanawa, H., Persons, D. A., and Nienhuis, A. W. (2005). Mobilization and mechanism of transcription of integrated self-inactivating lentiviral vectors. J. Virol. 79, 8410-8421.
66. Zaiss, A. K., Son, S., and Chang, L. J. (2002). RNA 3′ readthrough of oncoretrovirus and lentivirus: implications for vector safety and efficacy. J. Virol. 76, 7209-7219.
67. Bentley, D. L. (2005). Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors. Curr. Opin. Cell Biol. 17, 251-256.
68. Ramezani, A., Hawley, T. S., and Hawley, R. G. (2000). Lentiviral vectors for enhanced gene expression in human hematopoietic cells. Mol. Ther. 2, 458-469.
69. Zufferey, R., Donello, J. E., Trono, D., and Hope, T. J. (1999). Woodchuck hepatitis virus post transcriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J. Virol. 73, 2886-2892.
70. Loeb, J., Harris, M., and Hope, T. (2000). The woodchuck hepatitis virus post transcriptional regulatory element increases transgene expression by enhancing the 3'-end metabolism of mRNAs. Mol. Ther. 1 (Suppl. 1), S142.
71. Schambach, A., Bohne, J., Baum, C., Hermann, F. G., Egerer, L., von, L. D. et al. (2006). Woodchuck hepatitis virus post-transcriptional regulatory element deleted from X protein and promoter sequences enhances retroviral vector titer and expression. Gene Ther. 13, 641-645.
72. Ramezani, A. and Hawley, R.G. (2002) Overview of the HIV-1 lentiviral vector system, in Current Protocols in Molecular Biology (Ausubel, F., Brent, R., Kingston, B., Moore, D., Seidman, J., Smith, J. A., and Struhl, K., eds.), John Wiley & Sons, Inc., Somerset, NJ, pp. 16.21.1-16.21.15.
73. Ramezani, A. and Hawley, R.G. (2002) Generation of HIV-1-based lentiviral vector particles, in Current Protocols in Molecular Biology (Ausubel, F., Brent, R., Kingston, B., Moore, D., Seidman, J., Smith, J. A., and Struhl, K., eds.), John Wiley & Sons, Inc., Somerset, NJ, pp. 16.22.1-16.22.15.
74. Kelly, P. F., Vandergriff, J., Nathwani, A., Nienhuis, A. W., and Vanin, E. F. (2000). Highly efficient gene transfer into cord blood nonobese diabetic/severe combined immunodeficiency repopulating cells by oncoretroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein. Blood 96, 1206-1214.
75. Zufferey, R., Nagy, D., Mandel, R. J., Naldini, L., and Trono, D. (1997). Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat. Biotechnol. 15, 871-875.
76. Burns, J. C., Friedmann, T., Driever, W., Burrascano, M., and Yee, J.-K. (1993). 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. U. S. A. 90, 8033-8037.
77. Naldini, L., Blomer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H. et al. (1996). In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263-267.
78. Markowitz, D., Goff, S., and Bank, A. (1988). A safe packaging line for gene transfer: separating viral genes on two different plasmids. J. Virol. 62, 1120-1124.
79. Hanawa, H., Kelly, P. F., Nathwani, A. C., Persons, D. A., Vandergriff, J. A., Hargrove, P. et al. (2002). Comparison of various envelope proteins for their ability to pseudotype lentiviral vectors and transduce primitive hematopoietic cells from human blood. Mol. Ther. 5, 242-251.
80. Pear, W. S., Nolan, G. P., Scott, M. L., and Baltimore, D. (1993). Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. U. S. A. 90, 8392-8396.
81. Chen, S.-T., Iida, A., Guo, L., Friedmann, T., and Yee, J.-K. (1996). Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system. Proc. Natl. Acad. Sci. U. S. A. 93, 10057-10062.
82. Liu, M. L., Winther, B. L., and Kay, M. A. (1996). Pseudotransduction of hepatocytes by using concentrated pseudotyped vesicular stomatitis virus G glycoprotein (VSV-G)-Moloney murine leukemia virus-derived retrovirus vectors: comparison of VSV-G and amphotropic vectors for hepatic gene transfer. J. Virol. 70, 2497-2502.
83. Gallardo, H. F., Tan, C., Ory, D., and Sadelain, M. (1997). Recombinant retroviruses pseudotyped with the vesicular stomatitis virus G glycoprotein mediate both stable gene transfer and pseudotransduction in human peripheral blood lymphocytes. Blood 90, 952-957.
84. Hawley, R. G., Hawley, T. S., Fong, A. Z., Quinto, C., Collins, M., Leonard, J. P. et al. (1996). Thrombopoietic potential and serial repopulating ability of murine hematopoietic stem cells constitutively expressing interleukin 11. Proc. Natl. Acad. Sci. U. S. A. 93, 10297-10302.
85. Schambach, A., Galla, M., Modlich, U., Will, E., Chandra, S., Reeves, L. et al. (2006). Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical research. Exp. Hematol. 34, 588-592.
86. Hawley, T. S., Sabourin, L. A., and Hawley, R. G. (1989). Comparative analysis of retroviral vector expression in mouse embryonal carcinoma cells. Plasmid 22, 120-131.
87. Hawley, T. S., Herbert, D. J., Eaker, S. S., and Hawley, R. G. (2004). Multiparameter flow cytometry of fluorescent protein reporters. Methods Mol. Biol. 263, 219-238.
88. Hawley, R. G., Lieu, F. H., Fong, A. Z., and Hawley, T. S. (1994). Versatile retroviral vectors for potential use in gene therapy. Gene Ther. 1, 136-138.
89. Nucifora, G., Laricchia-Robbio, L., and Senyuk, V. (2006). EVI1 and hematopoietic disorders: history and perspectives. Gene 368, 1-11.
90. Hawley, R. G., Fong, A. Z. C., Lu, M., and Hawley, T. S. (1994). The HOX11 homeobox-containing gene of human leukemia immortalizes murine hematopoietic precursors. Oncogene 9, 1-12.
91. Eaker, S. S., Hawley, T. S., Ramezani, A., and Hawley, R. G. (2004). Detection and enrichment of hematopoietic stem cells by side population phenotype. Methods Mol. Biol. 263, 161-180.
92. Hawley, R.G., Ramezani, A., and Hawley, T.S. (2006) Hematopoietic stem cells, in Methods in Enzymology, Adult Stem Cells 419 (Lanza, R. and Klimanskaya, I., eds.), Elsevier/Academic Press, San Diego, CA. pp. 149-179.
93. Donahue, R. E., Sorrentino, B. P., Hawley, R. G., An, D. S., Chen, I. S. Y., and Wersto, R. P. (2001). Fibronectin fragment CH-296 inhibits apoptosis and enhances ex vivo gene transfer by murine retrovirus and human lentivirus vectors independent of viral tropism. Mol. Ther. 3, 359-367.
94. Moayeri, M., Ramezani, A., Morgan, R. A., Hawley, T. S., and Hawley, R. G. (2004). Sustained phenotypic correction of hemophilia A mice following oncoretroviral-mediated expression of a bioengineered human factor VIII gene in long-term hematopoietic repopulating cells. Mol. Ther. 10, 892-902.
95. Hawley, T. S., McLeish, W. A., and Hawley, R. G. (1991). Establishment of a novel factor-dependent myeloid cell line from primary cultures of mouse bone marrow. Cytokine 3, 60-71.
96. DuBridge, R. B., Tang, P., Hsia, H. C., Leong, P. M., Miller, J. H., and Calos, M. P. (1987). Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol. Cell. Biol. 1, 379-387.
97. Gorman, C. M., Gies, D., McCray, G., and Huang, M. (1989). The human cytomegalovirus major immediate early promoter can be trans-activated by adenovirus early proteins. Virology 171, 377-385.
98. Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D. et al. (1998). A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72, 8463-8471.
99. Higashikawa, F. and Chang, L. (2001). Kinetic analyses of stability of simple and complex retroviral vectors. Virology 280, 124-131.
100. Nightingale, S. J., Hollis, R. P., Pepper, K. A., Petersen, D., Yu, X. J., Yang, C. et al. (2006). Transient gene expression by nonintegrating lentiviral vectors. Mol. Ther. 13, 1121-1132.