Cytosine deaminase negative selection system for gene transfer t

Chemistry: molecular biology and microbiology – Spore forming or isolating process

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435 691, 435 701, 435227, 4352401, 4352523, 4353201, 536 221, 536 231, 536 232, 536 237, 536 2374, C12P 2106, C12N 500, C12N 978, C07H 2104

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053588665

ABSTRACT:
The present invention relates to a system comprising a modified bacterial gene for cytosine deaminase that has been engineered into a eukaryotic expression vector and the expression of the gene by mammalian cells.
The present invention further relates to methods, gene therapies and vaccines that employ the negative selectable marker, cytosine deaminase, which has the ability to produce a toxic antimetabolite 5-fluorouracil from 5-fluorocytosine.

REFERENCES:
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Nishiyama, T., et al.; "Neoplastic Effects in Rats of 5-Fluorocytosine in Combination with Cytosine Deaminase Capsules", Cancer Research, vol. 45, Apr. 1985, pp. 1753-1761.
Andersen, L., et al., Pryrimidine, Purine and Nitrogen Control of Cytosine Deaminase Synthesis In Escherichia coli K12 . . . , Arch Microbiol (1989) vol. 152, pp. 115-118.
Bennett, J. E., Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 8th Edition, (Pergamon Press New York) pp. 1165-1181.
Eglitis, M. A., et al., Gene Expression in Mice After High Efficiency Retroviral-Mediated Gene Transfer, Science (1985) vol. 230, pp. 1395-1398.
Eglitis, M. A., et al., Retroviral Vectors for Introduction of Genes Into Mammalian Cells, BioTechniques, (1988) vol. 6, pp. 608-614.
Moolten, F. L., et al., Curability of Tumors Bearing Herpes Thymidine Kinase Genes Transferred By Retroviral Vectors, J. Natl. Cancer Institute (1990) vol. 82, pp. 297-300.
Borrelli, E., et al., Targeting of an Inducible Toxic Phenotype in Animal Cell, Proc. Natl. Acad. Sci. USA (1988) vol. 85, pp. 7572-7576.
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