Polymer gel can block toxic leakage problem in gene therapy

DURHAM, N.C. -- Duke University biomedical engineers have devised a potentially patentable method to arrest toxic leakages of genetically engineered viruses that have plagued attempts to use gene therapy against cancerous tumors. The problem has been that viruses carrying anti-tumor genes have tended to leak from tumors, proving toxic to other body tissues.

The researchers have developed a biocompatible polymer that briefly changes from a liquid at 39 degrees Fahrenheit to a gel at body temperatures to block most gene-bearing viruses from being diverted through the blood stream to the wrong targets, the scientists reported in research journals.

"With this method we can reduce the misdirected virus dissemination by a factor of 100 to 1,000 times," said Fan Yuan, an associate biomedical engineering professor at Duke's Pratt School of Engineering who led the studies. "That's enough of a reduction to solve the problem."

The work was supported by the National Science Foundation.

According to Yuan, about 66 percent of the 918 gene therapy clinical trials conducted in 24 countries between 1989 and 2004 were aimed at treating cancer.

His interdisciplinary group from the Pratt School and the Duke Medical Center's radiation oncology department studied a preferred kind of anti-cancer gene therapy that uses relatively harmless adenoviruses to infect tumor cells. Once in a targeted tumor, genes in these genetically modified viruses are designed to express their modified genes to manufacture proteins that can either trigger tumor cell death or stimulate the immune system to attack the cancer.

Yuan said he and other Duke researchers have found that, because of the small size of pores in blood vessel walls and other access points, these adenoviruses cannot reach the majority of tumor cells by being injected into the blood stream but instead must be injected directly into tumors themselves.

However, direct intratumoral injectio

Contact: Monte Basgall
Duke University

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