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Abstract
The multiplexed cancer cell line screening platform PRISM demonstrated its utility in testing hundreds of cell lines in a single run, possessing the potential to speed up anti-cancer drug discovery, validation and optimization. Here we described the development and implementation of a next-generation PRISM platform combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated gene editing, cell line DNA barcoding and next-generation sequencing to enable genetic and/or pharmacological assessment of target addiction in hundreds of cell lines simultaneously. Both compound and CRISPR-knockout PRISM screens well recapitulated the results from individual assays and showed high consistency with a public database.
Highlights
The multiplexed cancer cell line screening platform PRISM demonstrated its utility in testing hundreds of cell lines in a single run, possessing the potential to speed up anti-cancer drug discovery, validation and optimization
Broad Institute’s Project Achilles through the DepMap portal offers the assessment of gene essentiality for the majority of protein-coding genes in >700 human cancer cell lines based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9- as well as RNA interference (RNAi)-mediated gene perturbation[4,5]
In order to enable the rapid validation of the therapeutic value of a given target of interest across a large panel of human cancer cell lines using both CRISPR and pharmacological perturbations, we developed BMS (Bristol Myers Squibb)-PRISM platform combining CRISPR/Cas9-mediated gene editing capability and DNA-barcoding multiplexing technique
Summary
The multiplexed cancer cell line screening platform PRISM demonstrated its utility in testing hundreds of cell lines in a single run, possessing the potential to speed up anti-cancer drug discovery, validation and optimization. We described the development and implementation of a next-generation PRISM platform combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated gene editing, cell line DNA barcoding and next-generation sequencing to enable genetic and/or pharmacological assessment of target addiction in hundreds of cell lines simultaneously. Both compound and CRISPRknockout PRISM screens well recapitulated the results from individual assays and showed high consistency with a public database. Both compound and CRISPR-knockout PRISM screens well recapitulated the results from individual assays and showed high consistency with public database
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