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'Stop leak' solution found for toxicity problems in experimental gene therapy

DURHAM, N.C. A Duke University research collaboration has identified a likely route for "leakage" of therapeutic gene-bearing viruses out of tumors in experimental anti-cancer gene therapy experiments in laboratory animals. The group also found this toxic leakage can be avoided by using a chemical extracted from common brown algae.

Their work was described in a 9:30 a.m. Sept. 8 presentation at the American Chemical Society's national meeting in New York, as well as in a research paper accepted for publication in the journal Molecular Cancer Therapeutics.

Investigators from the biomedical engineering department at Duke's Pratt School of Engineering and the radiation oncology department at the Duke Medical Center collaborated to trace why high concentrations of the protein produced by the therapeutic genes were present in the wrong places during animal experiments directed against tumors.

The experiments involved transplanting tumors into the legs of mice and then injecting those tumors with adenoviruses genetically altered to carry the cancer-fighting gene. About 24 hours after those adenoviruses infected the tumor cells, the virus-carried genes could then begin manufacturing a known anti-cancer protein called mouse interleukin-12 (IL-12).

When the researchers first tried the experiment using concentrations of IL-12 genes in the viruses they judged high enough to treat the cancer, "the animals died within 10 minutes," said Fan Yuan, a Duke associate professor of biomedical engineering, in an interview.

Exploring the reasons for the sudden deaths, the group used lower gene amounts that the animals could tolerate to trace what happened in their bodies during the extended infection and gene expression process.

They found that the virus preparations did not stay in the tumors as planned but also moved elsewhere in significant concentrations, principally to the liver.

The reason for that unanticipated migration was tumor blood ve
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Contact: Monte Basgall
monte.basgall@duke.edu
919-681-8057
Duke University
8-Sep-2003


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