Scientists from the University of California Berkeley continue to be ahead of the CRISPR game. Together with researchers at Massachusetts General Hospital and Harvard University, they have designed a more precise version of Cas9, the enzyme that cuts DNA. The result of their study is published in Nature.
The researchers identified a key region called REC3 in the Cas9 protein that governs how accurately CRISPR-Cas9 homes in on a target DNA sequence, and redesigned it with a hyper-accurate gene editor with the lowest level of off-target cutting to date.
“If you mutate certain amino acid residues in REC3, you can tweak the balance between Cas9 on-target activity and improved specificity; we were able to find the sweet spot where there is sufficient activity at the intended target but also a large reduction in off-target events,” said Janice Chen, one of the authors of the study and a graduate student in the lab of Jennifer Doudna, who co-invented the CRISPR-Cas9 gene-editing tool.
The hyper-accurate Cas9 or HypaCas9 has shown to retain its on-target efficiency, but is slightly better at discriminating between on- and off-target sites in human cells.
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