A third CRISPR-Cas platform for genome editing in human cells is presented in Nature Communications this week.

CRISPR-Cas9 is a versatile platform for genome editing, but it is not the only RNA-guided nuclease (an enzyme that cuts DNA) in the Cas family of proteins. In addition to Cas9, Cas12a and Cas12b have also been identified. Although Cas12a has been developed for genome editing, Cas12b has not been developed as thoroughly at least in part due to the high temperature requirements of this enzyme.

Feng Zhang and colleagues studied Cas12b since it is a smaller protein than either Cas9 or Cas12a, which makes it attractive for intracellular delivery via viral vectors. However, in its original structure the protein cuts the non-target strand of double-stranded DNA. To overcome this, the authors redesigned the protein for enhanced activity at body temperature (37°C). This redesigned protein displayed greater specificity to the desired target sequence compared to Cas9 in cell culture experiments.

Although more work needs to be done to develop the engineered Cas12b to be a widely applicable tool like Cas9, the addition of a potential third platform for genome editing expands the options available to the research community.