Feng Zhang, Broad Institute

developing a revolutionary genome tool

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developing a revolutionary genome tool


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One of the most revolutionary genomic technologies of our time started with a Wikipedia search.

Feng Zhang had just settled into his lab at the Broad Institute in 2011, where he was set to study diseases affecting the brain, when he overheard an infectious disease biologist talking about something called CRISPR. The naturally occurring segments of DNA helped bacteria cut bad DNA out of a cell nucleus to protect itself from infection.

Intrigued, Zhang plugged “CRISPR,” which stands for Clustered Regularly Interspaced Short Palindromic Repeats, into Wikipedia’s search bar to discover that some researchers had found ways to apply CRISPR to particular genes within bacteria, but they had not managed to use the technology on mammals.

Zhang decided to investigate. The young scientist, barely out of his 20s, had already invented another breakthrough technology called optogenetics, which controls neural activity in the brain with light and could lead to therapies for psychiatric and neurological problems. Two years later, while a post-doctoral fellow at Harvard, he had used another method, the TAL effector system, to activate or repress mammalian genes.


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requests for CRISPR reagents from around the world
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cost to use the previous genome editing technology (zinc-finger nucleases)
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cost to use CRISPR

Within two years of joining the team at the Broad Institute, Zhang found a way to apply CRISPR to the human genome, effectively creating a pair of gene “scissors” that could snip harmful pieces from a DNA strand and replace them with healthy ones.

For his discovery, Zhang was dubbed “DNA’s master editor” and “the Midas of methods”—with good reason. His CRISPR method was more precise and easier to use than earlier genome-editing methods, and Zhang readily shared his new tool with scientists around the world. Zhang’s eagerness to share the technology—a principle that underlies the Broad Institute’s work—dramatically increased the speed of scientific discovery.

“CRISPR is such a foundational research tool that it really does not make any sense to keep it closed or proprietary,” Zhang said. “One analogy might be that if you made programming languages for the web proprietary, it would be so much harder for the Internet to develop.”

The discoveries since Zhang published his research have been nothing short of transformative. Researchers around the world have used Zhang’s CRISPR technique to target harmful genes in animal models of cystic fibrosis, sickle cell anemia and autism. They have demonstrated that gene editing in mosquitoes could one day help fight the spread of malaria. Diseases could eventually be snipped out of human cells—from muscular dystrophy to HIV to cancer. Zhang has remained at the forefront of developing CRISPR, discovering that the method could turn genes “on” as well as “off,” and that it could be used to target multiple sites throughout an entire genome, crucial for studying complex ailments like cancer, which involves multiple genes.

CRISPR is a powerful enough technology that it has come under the scrutiny of esteemed scientists, led by Nobel Laureate David Baltimore. The scientists encouraged their peers to avoid human germline-editing experiments because of the potential dangers—an unethical trial, an accidental snip or insertion—and asked that civic leaders and the general public weigh in. The stakes are high financially, too, as the tool could lead to treatments worth billions of dollars.

In the meantime, there is still plenty for Zhang to explore—CRISPR offers clues about which genes play a part in disease, how cancer metastasizes, how tumors grow and, of special interest to Zhang, how neurological disorders like depression develop.

“Mental illnesses like depression or schizophrenia are some of the most debilitating diseases a person can have,” Zhang said. “By developing new technologies to help us understand the brain and the mechanisms of disease, I hope we can help tackle some of these problems.”


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