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DrugTargetSeqR: a genomics- and CRISPR-Cas9–based method to analyze drug targets
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DrugTargetSeqR: a genomics- and CRISPR-Cas9–based method to analyze drug targets
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Journal Article
DrugTargetSeqR: a genomics- and CRISPR-Cas9–based method to analyze drug targets
2014
Overview
Finding the biological targets of small molecules remains an important challenge in chemical biology and drug discovery. A method involving high-throughput sequencing, mutational analysis and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome editing identifies the targets and potential modes of compound resistance for two anticancer agents.
To identify physiological targets of drugs and bioactive small molecules, we developed an approach, named DrugTargetSeqR, which combines high-throughput sequencing, computational mutation discovery and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9–based genome editing. We applied this approach to ispinesib and YM155, drugs that have undergone clinical trials as anticancer agents, and uncovered mechanisms of action and identified genetic and epigenetic mechanisms likely to cause drug resistance in human cancer cells.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 38/70
/ 38/91
/ 631/553
/ Antineoplastic Agents - pharmacology
/ Cell Line, Tumor - drug effects
/ Clustered Regularly Interspaced Short Palindromic Repeats
/ Drug Resistance, Neoplasm - drug effects
/ Drug Resistance, Neoplasm - genetics
/ Genome
/ Genomics
/ High-Throughput Nucleotide Sequencing - methods
/ Humans
/ Mutation
