Conclusions
While some work remains to be done to establish that these new TK variants function firmly as super suicide genes in vivo, it is important to recognize that they contain multiple amino acid substitutions and would likely never be made by site-directed mutagenesis. Clearly, these results demonstrate the power of random sequence mutagenesis to tailor enzymes such as cytosine deaminase and HSV-1 thymidine kinase for gene therapy of cancers. Mutant HSV-1 TKs also hold promise for use in a wide variety of other applications including as a negative selectable marker for homologous recombination events for cell lineage ablation investigations and for tumor imaging by positron emission tomography. Random sequence mutagenesis coupled with positive genetic selection is a powerful means not only to investigate the contributions of a particular residue to function but also for the generation of enzymes with novel functions for numerous biomedical applications.
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Black, M.E. (2002). Enzyme and Pathway Engineering for Suicide Gene Therapy. In: Setlow, J.K. (eds) Genetic Engineering: Principles and Methods. Genetic Engineering, vol 23. Springer, Boston, MA. https://doi.org/10.1007/0-306-47572-3_7
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