SAFER CANCER GENE THERAPY A twist on a well-studied gene therapy may more safely melt tumors. In clinical trials, a herpes simplex gene encoding the enzyme thymidine kinase (TK) is delivered, via a retrovirus vector, to dividing brain cancer (glioma) cells. The infected cells produce TK, which kills them when the patient takes the anti-herpes drug ganciclovir. But viral vectors are risky--they can enter the nucleus during cell division and disrupt genes. Thomas Wagner, a distinguished professor of molecular and cellular biology at Ohio University in Athens, with researchers at Progenitor Inc. of Menlo Park, Calif., added the TK gene to a plasmid (a ring of DNA) called T7 (X. Chen et al., Human Gene Therapy, 9:729-36, 1998). The T7 vector never enters the nucleus, and it continuously produces the enzyme. "Expression is transient, just long enough to do what you want it to and it's gone....

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