CRISPR Rejiggered to Turn Genes On

Researchers modify the genome-editing tool to flip the switch on any gene they wish.

Dec 11, 2014
Kerry Grens

WIKIMEDIA, HIROSHI NISHIMASU ET AL. The CRISPR-Cas genome-editing system interferes with a target sequence of DNA, usually with the goal of inhibiting the expression of a gene or modifying its code. The Cas enzyme has been adjusted so that it can also activate genes, but the effect is far less robust. Feng Zhang of the Broad Institute and MIT and colleagues have now tweaked Cas so that it can upregulate any gene of interest, even those that have resisted previous attempts using CRISPR-Cas.

According to a study published this week (December 10) in Nature, Zhang’s group used structural data of the Cas9 enzyme to re-engineer it to include gene activation complexes in new sites. “Here we have shown that the . . . system is robust, specific, and can facilitate genome-scale gain-of-function screening when combined with a compact pooled [guide RNA] library,” the authors wrote in their report.

“If you use the older generation of tools, getting the technology to do what you actually want is a project on its own,” graduate student Silvana Konermann, the lead author of the study, said in a press release. “It takes a lot of time and is also quite expensive.”

The team then made a library of guide sequences to use with the CRISPR system to target any of the genes in the human genome. The researchers then deployed their new system to screen for genes involved resistance to a melanoma drug, finding new ones along with the usual suspects.