Abstract
Interferons were originally described as antiviral agents by Isaacs and Lindenmann (1). From its subtypes, fibroblast interferon (IFN-β) (2) was also found to have important cytostatic (3,4) as well as immunomodulatory functions (5) that have been advantageous for its clinical use both in cancer (6) and in autoimmune disease conditions such as multiple sclerosis (7,8) and, recently, in rheumatoid arthritis (9). As with many other cytokines, its local production is well controlled and environmental factors affect its expression. IFN-β has direct effects on the majority of cell types in the body, as its receptors are widely expressed in all tissues. Its use as a recombinant protein is limited because of its short half-life and production costs and its systemic delivery (subcutaneously) is inefficient, done at high doses and for long times using periodic administration. We and others have shown that the delivery of secreted biological compounds such as cytokines or their inhibitors (e.g., their soluble receptors) by gene therapy (10-13) can in a single administration achieve long-term therapeutic effects at doses that are various logs of magnitude lower than those used with protein therapy. Gene therapy could also be designed to deliver the gene product locally, or its transcriptional control could be engineered so that is regulated using exogenously added drugs (14). IFN-β, as some other cytokines (e.g., interleukin [IL]-4, IFN-γ) is species-specific, and in order to obtain appropriate biological responses in mice, we had to clone the mouse gene by polymerase chain reaction (PCR).
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References
Isaacs, A. and Lindenmann, J. (1957) Virus interference. I. The interferon. Proc. R. Soc. London Ser. B 147, 258–267.
Knight, E. (1976) Interferon: purification and initial characterization from human diploid cells. Proc. Natl. Acad. Sci. USA 73, 520–523.
Knight, E. J. (1976) Antiviral and cell growth inhibitory activities reside in the same glycoprotein of human fibroblast interferon. Nature 262, 302–303.
Einat, M., Resnitzky D., and Kimchi A. (1985) Close link between reduction of c-myc expression by interferon and, G0/G1 arrest. Nature 313, 597–600.
Devajyothi, C., Kalvakolanu, I., Babcock, G. T., Vasavada, H. A., Howe, P. H., and Ransohoff, R. M. (1993) Inhibition of IFN γ-induced MHC class II gene transcription by IFN β and Type β-1 transforming growth factor in human astrocytoma cells. J. Biol. Chem. 268, 18,794–18,800.
Liberati, A., De Angelis, V., Fizzotti, M., Schippa, M., Cecchini, M., Adiuto, D., et al. (1994) Natural-killer-stimulatory effect of combined low-dose interleukin-2 and IFN β in hairy-cell leukemia patients. Cancer Immunol. Immunother. 38, 323–331.
Arnason, B. G. W., Dayal, A., Qu,Z. X., Jensen, M. A., GenÁ, K., and Reder, A. T., eds. (1996) Mechanisms of Action of IFN β in Multiple Sclerosis. Springer Seminars in Immunopathology, Vol. 18, Springer-Verlag, Berlin, pp. 125–148.
Panitch, H. S. and Bever, C. T. (1993) Clinical trials of interferons in multiple sclerosis: what have we learned? J. Neuroimmunol. 46, 155–164.
Tak, P. P., ’t Hart, B. A., Kraan, M. C., Jonker, M., Smeets, T. J., and Breedveld, F. C. (1999) The effects of IFNβ treatment on arthritis. Rheumatology 38, 362–369.
Chernajovsky, Y., Adams, G., Podhajcer, O., Mueller, G., Robbins, P., and Feldmann, M. (1995) Inhibition of transfer of collagen-induced arthritis into SCID mice by ex-vivo infection of spleen cells with retroviruses expressing soluble human TNF receptor. Gene Ther. 2, 731–735.
Croxford, J. L., Triantaphyllopoulos, K., Podhajcer, O. L., Feldmann, M., Baker, D., and Chernajovsky, Y. (1998) Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system. J. Immunol. 160, 5181–5187.
Chernajovsky, Y., Adams, G., Triantaphyllopoulos, K., Ledda, M. F., and Podhajcer, O. L. (1997) Pathogenic lymphoid cells engineered to express TGF β 1 ameliorate disease in a collagen-induced arthritis model. Gene Ther. 4, 553–559.
Triantaphyllopoulos, K. A., Williams, R. O., Tailor, H. and Chernajovsky, Y. (1999) Amelioration of collagen-induced arthritis and suppression of IFN-γ, IL-12, and TNFα production by IFNb gene therapy. Arthritis Rheum. 42, 90–99.
Gould, D. J., Berenstein, M., Dreja, H., Ledda, F., Podhajcer, O. L., and Chernajovsky, Y. (2000) A novel doxycycline inducible autoregulatory plasmid which displays "e;on/off"e; regulation suited to gene therapy applications. Gene Ther. 7, 2061–2070.
Higashi, Y., Sokawa, Y., Watanabe, Y., Kawade, Y., Ohno, S., Takaoka, C., et al. (1983) Structure and expression of a cloned cDNA mouse IFN β. J. Biol. Chem. 258, 9522–9529.
Farrar, J., Smith, J., Murphy, T., Leung, S., Stark, G. and Murphy, K. (2000) Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse Stat2. Nat. Immunol. 1, 65–69.
Deonarain, R., AlcamÍ, A., Alexiou, M., Dallman, M., Gewert, D., and Porter, A. (2000) Impaired antiviral response and alpha/beta interferon induction in mice lacking β interferon. J. Virol. 74, 3404–3409.
Chernajovsky, Y., Mory, Y., Chen, L., Marks, Z., Novick, D., Rubinstein, M., et al. (1984) Efficient constitutive production of human fibroblast interferon by hamster cells transformed with the IFN-β 1 gene fused to an SV40 early promoter. DNA 3, 297–308.
Triantaphyllopoulos, K., Croxford, J. L., Baker, D., and Chernajovsky, Y. (1998) Cloning and expression of murine IFNb and a TNF antagonist for gene therapy of experimental allergic encephalomyelitis. Gene Ther. 5, 253–263.
Minor, P. (1985) Growth, assay and purification of picornaviruses, in Practical Approach (Mahy, B., ed.), IRL, Oxford, pp. 25–42.
Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.
Miller, E. J. (1972) Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry 11, 4903–4909.
Williams, R. O., Feldmann, M., and Maini, R. N. (1992) Anti-TNF ameliorates joint disease in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. USA 89, 9784–9788.
Sandri-Goldin, R. M., Goldin, A. L., Levine, M., and Glorioso, J. C. (1981) High-frequency transfer of cloned herpes simplex virus type 1 sequences to mammalian cells by protoplast fusion. Mol. Cell. Biol. 1, 743–752.
Wicks, I. P., Howell, M. L., Hancock, T., Kohsaka, H., Olee, T., and Carson, D. A. (1995) Bacterial lipopolysaccharide copurifies with plasmid DNA: implications for animal models and human gene therapy. Hum. Gene Ther. 6, 317–323.
Morgenstern, J. P. and Land, H. (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multipledrug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res. 18, 3587–3596.
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. USA 90, 8392–8396.
Almazan, G. and McKay, R. (1992) An oligodendrocyte precursor cell line from rat optic nerve. Brain Res. 579, 234–245.
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Chernajovsky, Y., Dreja, H., Triantaphyllopoulos, K., Gould, D. (2003). Interferon-β Gene Therapy for the Treatment of Arthritis. In: Körholz, D., Kiess, W. (eds) Cytokines and Colony Stimulating Factors. Methods in Molecular Biology, vol 215. Humana, Totowa, NJ. https://doi.org/10.1385/1-59259-345-3:171
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DOI: https://doi.org/10.1385/1-59259-345-3:171
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