RNA interference - genetically engineered mouse models(RNAi-GEMMs): a novel appro

DESCRIPTION (provided by applicant): An estimated 1.8 billion dollars is spent for each new successful drug developed, primarily in failed clinical trials due to lack of efficacy and safety. New approaches for rapid identification and early preclinical validation of novel therapeutic targets are crucial to make important go/no-go decisions and curb the cost of developing new cancer treatments. For decades, genetically engineered mouse models have provided a powerful platform to study disease initiation and maintenance, the tumor microenvironment and the responsiveness of cancers to known or novel therapeutics; however, the long lead times and high costs required to develop, intercross and maintain models with various cancer predisposing gene combinationshave limited their practical utility in the drug discovery process. RNA interference (RNAi), a mechanism that controls gene expression, can be exploited experimentally to silence nearly any gene target. By expressing synthetic short hairpin RNAs (shRN