Improving enzymes for cancer gene therapy

Nat Biotechnol. 1999 Feb;17(2):143-7. doi: 10.1038/6142.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Bone Marrow
  • Directed Molecular Evolution
  • Enzyme Therapy*
  • Enzymes / genetics
  • Genetic Therapy*
  • Humans
  • Neoplasms / therapy*
  • Prodrugs / metabolism


  • Enzymes
  • Prodrugs