siRNA Library Screening for Pharmacologic Radiation Mitigators

$395,776U19FY2012AINIH

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

Ionizing irradiation induces RNAs in cells which can be targeted prior to irradiation by siRNA to identify novel targets for radioprotector drugs. We have successfully used this strategy to identify a co,mmon drug, Glyburide, as a novel radioprotector. We now propose to apply this strategy to identify radiation mitigator drugs using radiosensitive human cell targets and siRNA screening after irradiation. The 1** Specific Aim will optimize and deploy sentinel cells for detecting RNA targets for new mitigator drugs. The second aim will be to use druggable siRNA libraries and small molecule libraries to identify radiation damage mitigators. The third aim will be to identify targets that interact positively with prioritized drugs to advance radiation mitigation effects.

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