The New Gene-Editing Technique That Reveals Cancer’s Weaknesses

“This is now the most powerful system we have in biology,” says Sabatini. “Any biological process we care about now, we can get the comprehensive set of genes that underlie that process. That was not possible before. There was no way one could imagine doing that.”

CRISPR involves two components—an enzyme called Cas9 that slices DNA, and a guide molecule that deploys Cas9 to the right target. Moffat and Sabatini’s teams both created libraries of guides, targeted to the majority of human genes. Both used the libraries to unleash Cas9 upon individual genes, to see if their loss would affect a cell’s ability to grow or reproduce. And both computed a kind of essentiality score to measure how critical the various genes are.

The two teams identified between 1,600 and 1,800 genes as being essential—around one in ten of the ones they analyzed. “It’s a big treasure chest of results,” says Moffat.Compared to their more dispensable peers, these genes are more strongly activated, and unlikely to carry disabling mutations. They’re more likely to have similar (and equally indispensable) counterparts in other species. And as Moffat puts it: “Essential genes like to hang out with each other.” That is, they build proteins that unite to form large collaborative complexes.Next Page

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