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Polymer gel can block toxic leakage problem in gene therapy

2005 issue of the journal Cancer Research the researchers proposed a solution to the viral escape problem in the form of a polymer compound already employed for wound healing and for drug and gene delivery.

After being mixed with a gene-bearing virus, this compound -- called poloxamer 407 -- undergoes a temporary phase change as its stiffens from a liquid to a gel state when warmed to body temperature, that study reported.

This 1,000-fold viscosity change only lasts 10 to 90 minutes, long enough to clog the escape route for large numbers of viruses so those will link up with and infect tumor cells instead, Yuan said.

The Duke team found the polymer-virus mixture "could reduce virus dissemination by two orders of magnitude (100 times) and significantly increase transgene expression in solid tumors," their study reported.

In comparative tests on breast tumors implanted in live mice, the authors noted that two mice in the group injected with adenoviruses without poloxamer died within a half hour after administration. "But mice in the poloxamer group did not show any problem," they wrote.

Additional studies using the glowing protein to trace viral dissemination showed that "the poloxamer solution could significantly reduce the transgene expression in the liver and increase the transgene expression in the tumor," they reported.

Yuan said he has applied for a provisional patent covering this new use of poloxamer 407, which his group purchased from the BASF Corp.

In 2003, Yuan, Wang, Krol, Li and other Duke researchers previously reported that another chemical extracted from common brown algae can also block toxic leakages from tumor injections when mixed with the adenoviruses. However, the high viscosity of that jello-like mixture made it hard to inject.

"The bottom line is that when people try to do gene therapy on cancer they must inject the genes into the tumor," Yuan said. "One way would be to try and in
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Source:Duke University


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