LAUSR

The CRISPR–Cas systems comprise two classes: multi-subunit effector class 1 and single-effector class 2. Class 2 systems, such as Cas9 and Cas12a, have been widely used as genomeediting tools. The more complicated class 1 systems, although accounting for the majority (about 90%) of CRISPR–Cas systems, have rarely been repurposed for genome editing. The reason behind the unpopularity is that class 1 systems rely on multiple Cas subunits to form a complex known as Cascade (CRISPR-associated complex for antiviral defense). Pickar-Oliver et al. explored type I variants of class 1 systems from Escherichia coli and Listeria monocytogenes. The expression and the formation of Cascade complexes are validated in bacterial cells and human cells. To demonstrate utility in human cells, they reprogrammed Cascade for targeted transcriptional modulation by tethering an activation domain or a repression domain to the Cascade complex. The multiple Cas subunits offer more options for fusing functional domains with improved flexibility. LT