Improving enzymes for cancer gene therapy

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...

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Bibliographic Details
Published in:Nature biotechnology 1999-02, Vol.17 (2), p.143-147
Main Authors: Loeb, Lawrence A, Encell, Lance P, Landis, Daniel M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biotechnology
Bone Marrow
Directed Molecular Evolution
Enzymes - genetics
Enzymes - therapeutic use
Fundamental and applied biological sciences. Psychology
Gene therapy
Genetic Therapy
Health. Pharmaceutical industry
Humans
Industrial applications and implications. Economical aspects
Neoplasms - therapy
Prodrugs - metabolism
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Summary: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.
ISSN:1087-0156
1546-1696
DOI:10.1038/6142