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Two teams worked closely to reveal the structural details of the Cas9 complex and to test their functional significance. Their efforts revealed a division of labor within the Cas9 complex. The researchers determined that the Cas9 protein consists of two lobes: One lobe is involved in the recognition of the RNA and DNA elements, while the other lobe is responsible for cleaving the target DNA, causing what is known as a “double strand break” that disables the targeted gene. The team also found that key structures on Cas9 interface with the guide RNA, allowing Cas9 to organize itself around the RNA and the target DNA as it prepares to cut the strands.
Identifying the key features of the Cas9 complex should enable researchers to improve the genome-editing tool to better suit their needs.
“Up until now, it has been very difficult to rationally engineer Cas9. Now that we have this structural information, we can take a principled approach to engineering the protein to make it more effective,” says Zhang, who is also a co-founder of Editas Medicine, a company that was started last year to develop Cas9 and other genome-editing technologies into a novel class of human therapeutics.