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Improving enzymes for cancer gene therapy

Nature Biotechnology volume 17, pages 143–147 (1999)Cite this article

Abstract

New techniques now make it feasible to tailor enzymes for cancer gene therapy. Novel enzymes with desired properties can be created and selected from vast libraries of mutants containing random substitutions within catalytic domains. In this review, we first consider genes for the ablation of tumors, namely, genes that have been mutated (or potentially can be mutated) to afford enhanced activation of prodrugs and increased sensitization of tumors to specific chemotherapeutic agents. We then consider genes that have been mutated to provide better protection of normal host tissues, such as bone marrow, against the toxicity of specific chemotherapeutic agents. Expression of the mutant enzyme could render sensitive tissues, such as bone marrow, more resistant to specific cytotoxic agents.

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Figure 1: Survival of alkyltransferase–deficient bacteria expressing wild–type or mutant 56–8 (Cys150→Tyr, Ser152→Arg, Ala154→Ser, Val155→Gly, Asn157→Thr, Val164→Met, Glu166→Gln, Ala170→Thr) AGT in the presence of MNNG ± BG (100 μM).

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Acknowledgements

We thank the investigators who made unpublished data available for this review. We also thank Ann Blank for helpful comments, and the referee and editors for valuable suggestions for the revised manuscript. L.A.L. is supported by NIH grant CA78885. L.P.E. is supported by a postdoctoral training grant from NIEHS (T32 ES07032), and D.M.L is supported by a medical scientist training grant from NIH NIGMS (5 T32 07266).

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  1. Departments of Pathology and Biochemistry, The Joseph Gottstein Memorial Cancer Research Laboratory, University of Washington School of Medicine, Box 357705, Seattle, 98195–7705, WA

    Lance P. Encell, Daniel M. Landis & Lawrence A. Loeb

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  1. Lance P. Encell
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Correspondence to Lawrence A. Loeb.

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Encell, L., Landis, D. & Loeb, L. Improving enzymes for cancer gene therapy. Nat Biotechnol 17, 143–147 (1999). https://doi.org/10.1038/6142

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