A key aspect of this proposal, embedded in each of the three research projects is the validation of predictions made by computational models of specific cellular programs involve in cancer progression. Those predictions need to be tested in cells and in animals by gain-of-function or loss of-function experiments. RNA interference (RNAi) has emerged as a novel cellular mechanism regulating gene expression at the posttranscriptional level and as a powerful tool to control gene function experimentally There have been several recent advances in the biology and application of RNAi. These include the definition of improved criteria for selecting effective small interfering RNA (siRNA) sequences ; improved methods for delivery of short interfering RNAs (siRNAs) or expression of short hairpin RNAs (shRNAs), which in turn generate siRNAs leading to stable silencing of genes in mammalian cells, tissues, and animals using retroviral expression systems. Both focused and high-throughput screening projects based on RNAi have been initiated to search for genes involved in basic biological processes, as well as in complex pathological conditions associated with cancer. The ICBP RNAi resource will develop new siRNA/shRNA delivery technologies and will provide support to the participants in this program that plan to use RNAi technologies in their research.
The specific aims of the RNAi resource facility are to: 1. Generate and distribute a set of functionally validated siRNAs and shRNAs that are able to silence genes of interest to the ICBP. 2. Develop and improve selection criteria for functional siRNA sequences. 3. Develop new approaches to achieve constitutive, regulated, or tissue-specific delivery of siRNAs and expression of shRNAs. 4. Provide technical and scientific advice to ICBP investigators on how to use RNAi technologies.
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