Bridge RNA-guided recombinases, which originate from the IS110 family of bacterial insertion sequence elements, show promise as programmable systems for genome editing. However, most work so far has been done in bacteria. Writing in Science, Pelea et al. provide insights into a bridge recombinase that can edit human cells.
Bridge recombinases act as editors by simultaneously recognizing their target and donor DNA using a bridge RNA. The bridge RNA sequence determines the specificity for both these substrates, yielding a versatile system for DNA deletion, inversion or insertion. The IS621 recombinase, which was previously shown to mediate a broad range of edits in bacterial cells, edited only 0.6% of human cells. The authors therefore screened more bridge recombinases for large-scale deletions in human cells and found ISCro4 to display the highest recombinase activity.
