CRISPR-Based Tool Maps Gene Function in Human Cells

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UC San Francisco scientists have used a high-throughput CRISPR-based technique to rapidly map the functions of nearly 500 genes in human cells, many of them never before studied in detail. 

The research generated a vast amount of novel genetic data, including identifying new genes involved in cellular energy production and explaining a long-standing mystery about why some cholesterol drugs can be used to treat osteoporosis while related drugs have no such effect. But the most important takeaway, the researchers say, is the novel framework the study demonstrates for comprehensively mapping the function of genes within human cells, which they hope to eventually extend to the whole human genome.

“We have a good understanding of the functions of about 1,000 to 2,000 critical human genes that – deservedly – have been very well studied,” said UCSF cancer biologist Luke Gilbert, PhD, one of the new study’s two senior authors. “But that’s less than 10 percent of the 25,000 genes in the human genome. Of the rest, perhaps half have been studied at least a little by someone, and the other half we know next to nothing about.”

“This is not surprising, because the experiments needed to test gene function are expensive and time consuming, so you need to prioritize the genes you think are probably the most important,” added Max Horlbeck, PhD, who recently completed his doctoral work in the lab of UCSF cell biologist Jonathan Weissman, PhD, the study’s second senior author. “But there are mysteries hiding in the rest of the genome that could lead to brand new treatments for a wide variety of diseases, and now we have a technique that can quickly and comprehensively map out how these unstudied genes fit into our broader understanding of biology.”

In their new study, published July 19, 2018, in Cell, Horlbeck and colleagues used a technique called genetic interaction mapping, which has been perfected in the …

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