Abstract
Retrovirus mediated gene transfer is one of the most powerful tools for the manipulation of a variety of cells. Beside its significance for the transduction of cultured cells for basic research and for biotechnology it has become a predominant method in gene therapy trials. Retroviral vectors provide a number of advantages compared to other transfer systems. However, the release of newly combined viruses with or without autonomous replication competence imposes higher safety conditions in handling such systems and makes them unacceptable in gene therapy. Here, we describe experimental systems which allow to define properties of cells, retroviral helper functions and retroviral vectors leading to the release of newly recombined retroviruses. The results allow us to estimate the safety of particular systems and to construct safer helper cells and vectors.
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References
Armentano D, Yu S-Y, Kantoff PW et al. (1987) Effect of internal viral sequences on the 114 utility of retroviral vectors. Virology 183: 611–619
Bender MA, Palmer TD, Gelinas RE, Miller AD (1987) Evidence that the packaging signal of moloney murine leukemia virus extends into the gag region. I Virol 61: 1639–1646
Bosselmann RA, Hsu R-Y, Bruszewski J, Hu S, Martin F, Nicoson M (1987) Replication defective chimeric helper proviruses and factors affecting generation of competent virus: expression of moloney murine leukemia virus structural genes via the metallothionein promoter. Mol Cell Biol 7: 1797–1806
Donahue RE, Kessler SW, Bodine D, McDonagh K, Dunbar C, Goodman S, Agricola B, Byrne E, Raffeld M, Moen R, Bacher J, Zsebo KM, Nienhuis AW (1992) Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. J Exp Med 176: 1125–1135
Jolly D (1994) Viral vectors systems for gene therapy. Cancer Gene Therapy 1: 51–64
Linial ML, (1987) Creation of a processed pseudogene by retroviral infection. Cell 49: 93–102.
Linial ML, Miller AD (1990) Retroviral RNA packaging: sequence requirements and implications, In: Swanstrom R and Vogt PK (cds.). Retroviruses: strategies of replication, Springer, Berlin p. 125–152
Luciw AP, Leung NJ (1992) Mechanisms of retrovirus replication. In: Levy JA (ed) The retroviridae. Plenum Press, New York London p159–298
Mann R, Baltimore D (1985) Varying the position of a retrovirus packaging sequence results in the encapsidation of both unspliced and spliced RNAs. J Virol 54: 401–407
Mann R, Mulligan RC, Baltimore D (1983) Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33: 153–159
Miller AD (1992) Retroviral vectors. In: Muzyczka N (ed.) Viral expression vectors. Springer, Berlin Heidelberg New York, p 1–24
Miller AD, Miller DG, Garcia JV, Lynch CM, (1993) Use of retroviral vectors for gene transfer and expression. Meth Enzymol 217: 581–599
Morgenstern JP, Land H (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res 18: 3587–3596
Nickoloff JA, Reynolds RJ (1990) Transcription stimulates homologous recombination in mammalian cells. Mol Cell Biol 10: 4837–4845
Nickoloff J A (1992) Transcription enhancers intrachromosomal homologous recombination in mammalian cells. Mol Cell Biol 12: 5311–5318
Otto E, Jones-Trower A, Vanin EF, Stambaugh K, Mueller SN, Anderson WF, McGarrity GJ (1994) Characterization of a replication-competent retrovirus resulting from recombination of packaging and vector sequences. Hum Gene Ther 5: 567–575
Scarpa M, Cournoyer D, Muzny DM, Moore KA, Belmont JW, Caskey CT (1991) Characterization of recombinant retroviruses from moloney-based vectors in ecotropic and amphotropic packaging cell lines. Virology 180: 849–852
Stuhlmann H, Jaenisch R, Mulligan RC (1989) Construction and properties of replication-competent murine retroviral vectors encoding methotrexate resistance. Mol Cell Biol 9: 100–108
Stuhlmann H, Dieckmann M, Berg P (1990) Transduction of cellular neo mRNA by retrovirus-mediated recombination. J Virol 64: 5783–5796
Torrent C, Wang P, Darlix J-L (1992) A murine leukemia virus derived retroviral vector with a rat VL30 packaging psi sequence. Bone Marrow Transplant 9: 143–147
Torrent C, Gabus C, Darlix J-L (1994) A small and efficient dimerization/packaging signal of rat VL30 RNA and its use in murine leukemia virus-VL30-dcrived vectors for gene transfer. J Virol 68: 661–667
Shinnick TM, Lerner RA, Sutcliffe JG (1981) Nucleotide sequence of Moloney murine leukaemia virus. Nature (London) 293: 543–548
Vanin EF, Kaloss M, Broscius C, Nienhuis AW (1994) Characterization of replication-competent retroviruses from nonhuman primates with virus-induced T-cell lymphomas and observations regarding the mechanism of oncogenesis. J Virol 68: 4241–4250
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© 1996 Springer-Verlag Berlin Heidelberg
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Klehr-Wirth, D., Wirth, M., Grannemann, R., Münk, C., Häuser, H. (1996). Accidental Formation of Replication-Competent Viruses from Gene Transfer by Retroviral Vectors. In: Schmidt, E.R., Hankeln, T. (eds) Transgenic Organisms and Biosafety. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61460-6_11
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DOI: https://doi.org/10.1007/978-3-642-61460-6_11
Publisher Name: Springer, Berlin, Heidelberg
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