Abstract
Recently, the treatment of human genetic disorders has been mediated by gene transfer technology especially for monogenic disorders. Further advances in gene therapy have become possible following the first successful treatment of patients deficient of the enzyme adenosine deaminase (ADA).1 This study explores the feasibility of using a defective non-replicating recombinant adenovirus vector to transfer a reporter gene (β-galactosidase) into neuronal cells. By their nature viruses efficiently transfer their genes to cells and promote expression of their encoded gene products in a precise and predetermined fashion. This property has been exploited to construct a replication-deficient adenoviral vector (RAd35).2 Unlike some other expression systems, defective adenoviral vectors grow to a high titre in a helper cell line (293 cells)3 and provide high levels of protein expression from a strong constitutive human viral promoter.4
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References
French-Anderson, W. (1992) Human Gene Therapy. Science 256, 808–814.
Wilkinson, G.W.G., & Akrigg., A. (1992) Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector. Nucleic Acids Res. 20, 2233–2239.
Racher, A.J., Fooks, A.R. and Griffiths, J.B. (1995) Culture of 293 cells in different culture systems: Cell growth and recombinant adenovirus production. Biotechnology Techniques 9, (3); 169–174.
Fooks, A.R., Schadeck, E., Liebert, U.G., Dowsett, A.B., Rima, B.K., Steward, M., Stephenson, J.R. & Wilkinson G.W.G. (1995) High-level expression of the measles virus nucleocapsid protein by using a replication-deficient adenovirus vector: Induction of an MHC-1-Restricted CTL response and protection in a murine model. Virology 210, 456–465.
Warnes, A., & Fooks, A.R. (1996) Live Viral vectors: Construction of a replication-deficient recombinant adenovirus. In: Vaccine Protocols (A. Robinson, G. Farrar and C. Wiblin, Eds). pp. 33–45, “Methods in Molecular Medicine Series” Chapman and Hall, London, UK.
Wilkinson, G.W.G. and Akrigg, A. (1991) The cytomegalovirus major immediate early promoter and its use in eukaryotic expression systems. Adv.Gene.Tech. 2, 287–310.
Bert., A.J., Krougliak, V., & Graham., F.L. (1995) DNA sequence of the deletion/insertion in early region 3 of Ad5 dl309. Virus Research 39, 75–82.
McGrory, W.J., Bautista, D.S. & Graham, F.L. (1988). A simple technique for the rescue of early region I mutations into infectious human adenovirus type 5. Virology 163, 614–617.
Schindler, C., Fooks, A.R., Stephenson, J.R. & Liebert, U.G. (1994) Replication-incompetant adenoviruses as vectors for protective immunization against measles virus infection. Behring Inst.Mitt, 95, 109–115.
Top, F.H., Buescher, E.L., Bancroft, W.H. & Russell, P.K. (1971) Immunization with live types 7 and 4 adenovirus vaccines. II. Antibody response and protective effect against acute respiratory disease due to adenovirus type 7. J.Infect.Dis. 124, 155–160.
Crystal, R.G., McElvaney, N.G., Rosenfield, M.A., Chu, C-S., Mastrangeli, A., Fay, J.G., Brody, S.L., Jaffe, H.A., Eissa, N.T., & Danel, C. (1994) Administartion of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nature Genetics 8, 42–51.
Lowenstein, P.R., Wilkinson, G.W.G., Castro, M.G., Shering, A.F., Fooks, A.R. & D. Bain. (1996) Non-neurotropic adenovirus: a vector for gene transfer to the brain and possible gene therapy of neurological disorders. In: Genetic manipulation of the nervous system, (edited by Prof. D.S. Latchman), pp.11–32, “Neuroscience Perspectives Series” Academic Press, London, UK.
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© 1997 Springer Science+Business Media Dordrecht
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Sivasubramaniam, S.D., Fooks, A.R., Lee, J., Stacey, G., Jennings, A.D. (1997). Neurological Therapy — Adenovirus Mediated Gene Therapy in Cells of the Central Nervous System. In: Carrondo, M.J.T., Griffiths, B., Moreira, J.L.P. (eds) Animal Cell Technology. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5404-8_9
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DOI: https://doi.org/10.1007/978-94-011-5404-8_9
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