A new enzyme named xCas9 allows researchers to target more sites in the genome than with traditional CRISPR-Cas9 editing, while also reducing off-target effects. The technique was reported earlier this year (February 28) by a biologist David Liu and his colleagues.
CRISPR-Cas9 has become the gene-editing tool of choice in many labs due to the effectiveness and convenience. But CRISPR-Cas9 has limitations like the necessity of targeting a particular sequence called a PAM near the gene to be modified, which limits researchers’ ability to make specific genetic changes.
“Relief from the PAM restriction is quite important,” Albert Jeltsch of the University of Stuttgart in Germany. “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. It just so happens that xCas9 also turned out to be more specific to the targeted sites, with fewer off-target effects. xCas9 will allow gene therapy to have higher success rates.