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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The expression of bacterial nitroreductase in transgenic mice results in specific cell killing by the prodrug CB1954.

The enzyme nitroreductase, isolated from Escherichia coli B, converts CB1954 ((5-aziridin-1-yl)-2,4-dinitro-benzamide) into a cytotoxic DNA interstrand cross-linking agent. The E. coli B gene (nfnB, NTR) encoding nitroreductase (NTR) was cloned into eukaryotic expression vectors. When driven by a CMV promoter, 5-10% of the stably transfected mouse fibroblasts expressed the NTR enzyme. These cells were killed at a concentration of 20 microM CB1954 in comparison to nonexpressing cells which were killed at a much higher concentration (500 microM). We subsequently generated transgenic mice to test the prodrug system in vivo. Nitroreductase was expressed specifically in T cells driven by the control elements of the human CD2 locus. Upon CB1954 treatment, transgenic mice show extensive cell depletion in thymus and spleen (14-16% of normal cell numbers), whereas all other tissues are unaffected by prodrug administration. These results raise the possibility of using the NTR gene in anticancer therapy.[1]


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