"This is very impressive and important work," University of Massachusetts Medical School molecular biologist Erik Sontheimer tells Science.
Though relatively new, CRISPR-Cas9 has become the gene-editing tool of choice in many labs due to its power, ease of use, and versatility. But it does have some notable limitations, as detailed by a Nature news article, including the necessity of targeting a particular sequence called a PAM near the gene to be modified, which limits researchers’ ability to make very specific genetic changes.
“Relief from the PAM restriction is quite important,” Albert Jeltsch of the University of Stuttgart in Germany tells Nature. “Some of these elements are quite small, and then the restriction can be quite relevant.”
Liu and his colleagues used a laboratory technique to evolve an enzyme that could recognize a broader range of PAM sequences, enabling more sites in the genome to be targeted than is possible with the original Cas9. Surprisingly, they write, xCas9 also turned out to be more specific to the targeted sites, with fewer off-target effects.