WIKIMEDIA, CHAOS

Using the CRISPR/Cas9 genome-editing system to mutate the gene regions encoding particular protein domains could result in a new and more efficient method to screen for druggable protein targets critical to the survival of cancer cells, according to a study published this week (May 11) in Nature Biotechnology.

Current CRISPR-based screens often mutate the beginning of a gene, which sometimes results in the expression of a functional protein variant. To circumvent this problem, researchers at Cold Spring Harbor Laboratory (CSHL) designed CRISPR guide RNAs that would mutate the portion of a gene encoding a domain on the surface of the protein where a small molecule could bind to alter the protein’s function. The team had previously identified such a binding pocket on the protein BRD4, and a small molecule inhibitor that binds in the pocket is an effective leukemia treatment.

In the latest study, the researchers targeted...

“If you change the pocket so the protein is no longer functional and you find the cancer can’t survive, then you have a good shot at a useful drug target,” study coauthor Christopher Vakoc of CSHL said in a statement. “More broadly, what we provide is a way to comprehensively identify specific vulnerabilities in cancer cells, across cancer types.”

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