Abstract
A number of phosphodiesterases, some of which possess additional biological activities (e.g., antitumor, immunosupressive, and so on), have been considered for use in targeted tumor therapy. We propose Deoxyribonuclease I (DNase I), a compact, monomeric enzyme, as a very attractive candidate for targeting to tumor cells. Only a small amount of enzyme targeted to a cell needs to enter the nucleus in order to degrade the chromosomal DNA, making a cell incapable of further replication. We describe preliminary data on the construction of a potent single-chain antibody (scFv) immunotoxin based on bovine pancreatic DNase I. The use of a mammalian enzyme should be much less toxic and less immunogenic than current immunotoxins and may expand the current limits of immunotoxin therapy.
Similar content being viewed by others
References
Rybak, S. M., Hoogenboom, H. R., Meade, H. M., et al. (1992)Proc. Natl. Acad. Sci. USA 89, 3165–3169.
Oefner, C. and Suck, D. (1986)J. Mol. Biol. 192, 605–632.
Weston, S. A., Lahm, A., and Suck, D. (1992)J. Mol. Biol. 226, 1237–1256.
Laskowski M., Sr. (1971)The Enzymes, 3rd. ed., vol. 3 (Boyer, P. D., ed.), Academic, New York, pp. 289–311.
Peitsch, M. C., Polzar, B., Stephan, H., et al. (1993)EMBO J. 12, 371–377.
Hubbard, R. C., McElvaney, Birrer, P., et al. (1992)N. Engl. J. Med. 326, 812–815.
Worall, A. F. and Connolly, B. A. (1990)J. Biol. Chem. 265, 21,889–21,895.
Savage, P., Rowlinson-Busza, G., Verhoyen, M., So., A. Spooner, R. A., and Epenetos, A. A. (1993)Br. J. Cancer, submitted.
Epenetos, A. A., Travers, P., Gatter, K. C., Oliver, R. D. T., Mason, D. Y., and Bodmer, W. F. (1984)Br. J. Cancer 49, 11–15.
Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989)Molecular Cloning: A Laboratory Manual (2nd ed.), Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Garcia-Bustos, J., Heitman, J., and Hall, M. N. (1991)Biochim. Biophys. Acta 1071, 83–101.
Kalderon, D., Roberts, B. L., Richardson, W. D., and Smith, A. E. (1984)Cell 39, 499–509.
Lanford, R. E., Kanda, P., and Kennedy, R. C. (1986)Cell 46, 575–582.
Yoneda, Y., Semba, T., Kaneda, Y., Noble, R., et al. (1991)Exp. Cell. Res. 201, 313–320.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Linardou, H., Deonarain, M.P., Spooner, R.A. et al. Deoxyribonuclease I (DNase I). Cell Biophysics 24, 243–248 (1994). https://doi.org/10.1007/BF02789235
Issue Date:
DOI: https://doi.org/10.1007/BF02789235