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Polymer gel can block toxic leakage problem in gene therapy

ene-bearing viruses to escape their intended target and pose risks elsewhere, the researchers found in a study the researchers reported in the April 2005 issue of the British Journal of Cancer.

In that study, the researchers injected adenoviruses that produce glowing proteins in order to trace where the viral particles went during 24 hours after being injected into breast tumors implanted in experimental mice.

That investigation showed that 10 times more of the viral particles were transported to other organs than were retained within the tumors. And most of the errant viruses ended up in the liver, where the gene therapy protein products could cause cell death. Moreover, most viruses escaped from their intended tumor targets during the first 10 minutes.

Prompted by reports of animal deaths during past gene therapy trials with adenoviruses, this study provided the first direct research evidence that therapeutic gene-bearing viruses were being disseminated away from the tumor site via the blood stream, Yuan said. "In the past people wouldn't admit that," he said. "Nobody in the gene therapy field would believe this was happening."

The study also pinpointed the routes for the viral escapes. Those particles were escaping from the tumor area into the bloodstream through rifts in tiny tumor blood vessels created by damage from the injection needle.

Yuan said such viral escapes are inevitable since the needle's diameter is 30 times larger than the width of the microvessels that supply the tumor with blood. The needle is also wider than the spaces between each of those vessels, he added.

The first author of the British Journal of Cancer study was Yuan's graduate student Yong Wang. Other authors included Yuan, Yuan's research associate Ava Krol, associate research professor of radiation oncology Chuan-Yuan Li, and radiation oncology research associates Shanling Liu and Takashi Kon.

In a followup study in the September
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Source:Duke University


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