Summary
Advances in gene technology and cell biology have supplied the means to undertake human gene therapy in the near future. Techniques have been developed for the efficient introduction of gene sequences into the pluripotential stem cells of the haematopoietic system and our increased understanding of gene-regulatory mechanisms should allow therapeutic gene expression levels to be obtained.
Gene therapy should, at present, be termed gene supplementation since it will involve the addition of corrective genes to the host cell genome. It may only be used to treat recessively inherited disorders. Prospects for the future include the use of homologous recombination to correct or replace defective genes, allowing the treatment of dominantly inherited diseases.
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References
Brownlee, G. G. Towards gene therapy for haemophilia B. MRC News 39 (1988) 14–15
Chang, S. M. W., Wager-Smith, K., Tsao, T. Y., Henkel-Tigges, J., Vaishnav, S. and Caskey, C. T. Construction of a defective retrovirus containing the human hypoxanthine phosphoribosyltransferase cDNA and its expression in cultured cells and mouse bone marrow. Mol. Cell. Biol. 7 (1987) 854–865
Chu, G., Hayakawa, H. and Berg, F. Electroporation for the efficient transfection of mammalian cells with DNA. Nucl. Acids Res. 15 (1987) 1311–1326
Dzierzak, E. A., Papayannopoulou, T. and Mulligan, R. C. Lineage-specific expression of a human ß-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells. Nature 331 (1988) 35–41
Grosveld, F., van Assendelft, G. B., Greaves, D. R. and Kollias, G. Position-independent, high-level expression of the human 13-globin gene in transgenic mice. Cell 51 (1987) 975–985
Higuchi, R., von Beroldingen, C. H., Sensabaugh, G. F. and Erlich, H. A. DNA typing from single hairs. Nature 332 (1988) 543–546
Hock, R. A. and Miller, A. D. Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells. Nature 320 (1986) 275–277
Hogan, B., Costantini, F. and Lacy, E. Manipulating the Mouse Embryo: A laboratory manual, Cold Spring Harbor Laboratory, 1986
Lemischka, I. R., Raulet, D. H. and Mulligan, R. C. Developmental potential and dynamic behaviour of haematopoietic stem cells. Cell 45 (1986) 917–927
Mann, R., Mulligan, R. C. and Baltimore, D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33 (1983) 153–159
Miller, A. D., Echner, R. J., Jolly, D. J., Friedmann, T. and Verma, I. M. Expression of a retrovirus encoding human HPRT in mice. Science 225 (1984) 630–632
Parkman, R. The application of bone-marrow transplantation to the treatment of genetic diseases. Science 232 (1986) 1373–1378
Readhead, C., Popko, B., Takahashi, N., Shine, H. D., Saavedra, R. A., Sidman, R. L. and Hood, L. Expression of a myelin basic protein gene in transgenic shiverer mice: Correction of the dysmyelinating phenotype. Cell 48 (1987) 703–712
Robertson, M. Desperate appliances. Nature 320 (1986) 213–214
Smithies, O., Gregg, R. G., Boggs, S. S., Koralewski, M. A. and Kucherlapati, R. S. Insertion of DNA sequences into the human chromosomal ß-globin locus by homologous recombination. Nature 317 (1985) 230–234
Thomas, K. R. and Cappechi, M. R. Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene. Nature 324 (1986) 34–38
Thomas, K. R., Folger, K. R. and Capecci, M. R. High frequency targeting of genes to specific sites in the mammalian genome. Cell 44 (1986) 419–428
Walters, L. The ethics of human gene therapy. Nature 320 (1986) 225–227
Williams, D. A., Lemischka, I. R., Nathan, D. G. and Mulligan, R. C. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature 310 (1984) 476–480
Williams, D. A., Orkin, S. H. and Mulligan, R. C. Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. Proc. Natl. Acad. Sci USA 83 (1986) 2566–2570
Yu, S-F., von Ruden, T., Kantoff, P. W., Garber, C., Seiberg, M., Ruther, U., Anderson, W. F., Wagner, E. F. and Gilboa, E. Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc. Natl. Acad. Sci. USA 83 (1986) 3194–3198
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© 1989 SSIEM and Kluwer Academic Publishers
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Akhurst, R.J. (1989). Prospects for Gene Therapy Now and in the Future. In: Addison, G.M., Connor, J.M., Harkness, R.A., Pollitt, R.J. (eds) Studies in Inherited Metabolic Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1069-0_14
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DOI: https://doi.org/10.1007/978-94-009-1069-0_14
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