Abstract
Genetic disorders affecting the central nervous system (CNS) can potentially be treated by gene transfer using vectors which infect and express genes in post–mitotic neurons. Herpesviruses establish latent infections in neurons during which only one viral gene (LAT) is expressed, thus the LAT promoter may express foreign genes in latently infected CNS cells. Expression of a β–glucuronidase gene driven by the LAT promoter was tested in mice lacking this enzyme, which are a model for a human genetic disease affecting the CNS (mucopolysaccharidosis VII, Sly disease). Cells expressing the missing enzymatic activity were present in the trigeminal ganglia and brainstems of latently infected animals, up to four months post–inoculation, demonstrating the potential of this approach for the long–term expression of foreign genes in the CNS.
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References
Sly, W.S., Quinton, B.A., McAlister, W.H. & Rimoin, D.L. J. Pediatr. 82, 249–257 (1973).
Neufeld, E.F. & Muenzer, J. The Metabolic Basis of Inherited Disease 6th edn (eds Scriver, C.R., Beaudet, A.L., Sly, W.S. & Valle, D.) 1565–1587 (McGraw Hill, New York, 1989).
Birkenmeier, E.H. et al. J. clin. Invest. 83, 1258–1266 (1989).
Haskins, M.E., Desnick, R.J., DiFerrante, N., Jezyk, P. & Patterson, D.F. Ped. Res. 18, 980–984 (1984).
Wolfe, J.H. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2877–2881 (1990).
Stramm, L.E. et al. Exptl. eye Res. 50, 521–532 (1990).
Smith, B.F., Hoffman, R.K., Giger, U. & Wolfe, J.H. Molec. cell. Biol. 10, 3268–3271 (1990).
Rosenberg, M.B. et al. Science 242, 1575–1578 (1988).
Price, J., Turner, D.L. & Cepko, C.L. Proc. natn. Acad. Sci. U.S.A. 84, 156–160 (1987).
Ho, D.Y. & Mocarski, E.S. Virology 167, 279–283 (1988).
Palella, T.D. et al. Molec. cell. Biol. 8, 457–460 (1988).
Geller, A.I. & Breakefield, X.O. Science 241, 1667–1669 (1988).
Stevens, J.G. Microbiol. Rev. 53, 318–332 (1989).
Fraser, N.W. et al. Curr. eye Res. 10s, 1–13 (1991).
Deshmane, S.L. & Fraser, N.W. J. Virol. 63, 943–947 (1989).
Deatly, A.M., Spivack, J.G., Lavi, E. & Fraser, N.W. Proc. natn. Acad. Sci. U.S.A. 84, 3204–3208 (1987).
Stevens, J.G., Wagner, E.K., Devi-Rao, G.B., Cook, M.L. & Feldman, L.T. Science 235, 1056–1069 (1987).
Spivack, J.G. & Fraser, N.W. J. Virol. 62, 1479–1485 (1988).
Farrell, M.J., Dobson, A.T. & Feldman, L.T. Proc. natn. Acad. Sci. U.S.A. 88, 790–794 (1991).
Mitchell, W.J. et al. J. gen. Virol. 71, 953–957 (1990).
Steiner, I., Spivak, J.G., O'Boyle, D.R., Lavi, E. & Fraser, N.W. J. Virol. 62, 3493–3496 (1988).
Leib, D.A. et al. J. Virol. 63, 2893–2900 (1989).
Steiner, I. et al. EMBO J. 8, 505–511 (1989).
Izumi, K.M., McKelvey, A.M., Devi-Rao, G., Wagner, E.K. & Stevens, J.G. Microbial Pathogen. 7, 121–134 (1989).
Ho, D.Y. & Mocarski, E.S. Proc. natn. Acad. Sci. U.S.A. 86, 7596–7600 (1989).
Dobson, A.T. et al. J. Virol. 63, 3844–3851 (1989).
Deatly, A.M., Spivack, J.G., Lavi, E., O'Boyle, D.R. & Fraser, N.W. J. Virol. 62, 749–756 (1988).
Block, T.M. et al. J. Virol. 64, 3417–3426 (1990).
Fishman, W.H., Baker, J.R. & Goldman, S.S. Nature 213, 457–460 (1967).
Birkenmeier, E.H. et al. Blood 78, 3081–3092 (1991).
Olsen, L., Dean, M.F., Harris, G. & Muir, H., Nature 291, 244–247 (1981).
Friedmann, T. Science 244, 1275–1281 (1991).
Dobson, A.T. et al. Neuron 5, 353 (1990).
Schull, R.M., Breider, M.A. & Constantopoulos, G.C. Ped. Res. 24, 347–352 (1988).
Nishimura, Y. et al. Proc. natn. Acad. Sci. U.S.A. 83, 7292–7296 (1986).
Pignatti, P.F., Meneguzzi, G., Chenciner, N. & Milanesi, G. Virology 93, 260–264 (1979).
Roizman, B. Cell 16, 481–494 (1979).
Perry, L.J. & McGeoch, D.J. J. gen. Virol. 69, 2831–2846 (1988).
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Wolfe, J., Deshmane, S. & Fraser, N. Herpesvirus vector gene transfer and expression of β–glucuronidase in the central nervous system of MRS VII mice. Nat Genet 1, 379–384 (1992). https://doi.org/10.1038/ng0892-379
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DOI: https://doi.org/10.1038/ng0892-379
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