-CORE B Core B supports every project within the Program by providing access to state-of-the-art CRISPR-Cas9 and RNAi tools. Short hairpin RNAs (shRNAs) were developed with the support of this program, and ongoing innovations by Core B and Program investigators have helped to make these extremely powerful biological tools. During the past funding period, the Core devised a novel algorithm for predicting shRNA potency, which led to the generation of a 5th version of RNAi libraries corresponding to annotated protein coding genes in humans and mice. Technology has also been developed for using CRISPR-Cas9 screening to expose functionally important protein domains. During the upcoming period of requested support, the Core proposes to aid Program investigators through five general aims. First, the program will continue providing access to state- of-the-art RNAi vectors and CRISPR-Cas9 vectors and procedures for analyzing either single gene knockdowns or for performing pooled RNAi/CRISPR screens. Second, the Core will provide Program investigators with access to the mouse and human version 5 shRNA library and will compile sub-libraries upon request. Third, the Core will construct custom CRISPR-scanning libraries for performing structure-function analysis on genes of interest within each Program. Fourth, the Core will produce custom domain-focused CRISPR libraries to allow for interrogation and discovery cancer drug targets in various contexts. Fifth, the Core will carry on its efforts to improve CRISPR-Cas9 technologies, and make those innovations available to the Program and to the scientific community at large.

Public Health Relevance

- CORE B Core B will provide Program investigators with a suite of newly developed genetic tools for studying basic molecular mechanisms and for exposing novel vulnerabilities in cancer cells. In particular, the CRISPR-Cas9 methodology provided in this Core provides an innovative method for cancer drug target discovery and exposing functional domains of protein and non-coding RNAs.

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National Cancer Institute (NCI)
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Cold Spring Harbor Laboratory
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