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Massive gene screening points way to more effective chemotherapy

The tiny bits of RNA used are called small interfering RNA, or siRNA. In this experiment, four siRNAs targeting a single gene were placed in each well. Overall, the researchers used 84,508 different siRNAs.

Next, the drug paclitaxel was added to each well for two days. By examining the survival of the cells in each well, the researchers determined which genes were involved in affecting the cells sensitivity to the drug.

All told, the experiment took more than 150,000 individual pipetting steps over seven weeks to test the drug.

The researchers then re-tested the six genes that showed the most dramatic effect with paclitaxel and tried the same test using the chemotherapy drugs vinorelbine (Navelbine) and gemcitabine (Gemzar), but the results were not as dramatic as those seen for paclitaxel. "Our studies using additional drugs indicate that the genes we uncovered are highly specific for paxlitaxel," said Dr. Angelique Whitehurst, postdoctoral researcher in cell biology and lead author of the study.

"Being able to do this in human cells, and being able to do it fast this is very powerful," Dr. White said. "The idea of the screen was to be able to take advantage of the new generation of technology to silence any gene we want. Thats the power of a genome-wide screen you go in without any expectations and let the data tell you whats important."


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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
11-Apr-2007


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