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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

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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. So it is ...

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