Identification of a novel NAMPT inhibitor by CRISPR/Cas9 chemogenomic profiling in mammalian cells
Scientific Reports2017Vol. 7(1), pp. 42728–42728
Citations Over TimeTop 10% of 2017 papers
David Estoppey, Jeffrey Hewett, Chantale T. Guy, Edmund Harrington, Jason R. Thomas, Markus Schirle, Rachel Cuttat, Annick Waldt, Bertran Gerrits, Zinger Yang, Sven Schuierer, Xuewen Pan, Kevin Xie, Walter Carbone, Judith Knehr, Alicia Lindeman, Carsten Russ, Elizabeth Frias, Gregory R. Hoffman, Malini Varadarajan, Nadire Ramadan, John Reece-Hoyes, Qiong Wang, Xin Chen, Gregory McAllister, Guglielmo Roma, Tewis Bouwmeester, Dominic Hoepfner
Abstract
Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets and the mechanism of bioactive compounds. Until recently, genome-wide, high-resolution experiments of this nature have been limited to fungal systems due to lack of mammalian genome-wide deletion collections. With the example of a novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, we demonstrate that the CRISPR/Cas9 system enables the generation of transient homo- and heterozygous deletion libraries and allows for the identification of efficacy targets and pathways mediating hypersensitivity and resistance relevant to the compound mechanism of action.
Related Papers
- → Unintended CRISPR-Cas9 editing outcomes: a review of the detection and prevalence of structural variants generated by gene-editing in human cells(2023)99 cited
- → CRISPR–Cas9 gene editing induced complex on-target outcomes in human cells(2022)34 cited
- → Challenges of in vitro genome editing with CRISPR/Cas9 and possible solutions: A review(2020)29 cited
- → CRISPR/Cas9 system: A promising technology for the treatment of inherited and neoplastic hematological diseases(2018)17 cited
- → Strategies for Optimization of the Clustered Regularly Interspaced Short Palindromic Repeat-Based Genome Editing System for Enhanced Editing Specificity(2021)2 cited