A molecular oddity found in bacteria could hold the key to redesigning genomes at will, allowing researchers to insert, delete or flip large segments of DNA.

Enzymes in the IS110 family use a complex and unusual RNA-based targeting system, the team found. One end of the RNA binds to a piece of the DNA that will be inserted into the genome and the other end binds to a DNA snippet at the site in the genome where the cargo will go. Because the RNA bridges the two DNA segments, the team dubbed these molecules ‘bridge RNAs’.

By changing the sequences at either end of this bridge, the researchers were able to program IS110 enzymes to insert a cargo of their choosing where they wanted in the genome. They used the system to precisely insert a piece of DNA that was nearly 5,000 bases long into the genome of the bacterium Escherichia coli, and to excise and invert another piece of DNA from the E. coli genome.

The work on IS110 and IS1111 is “beautiful”, Long says. “But I really hope that in a few months, they’ll say it’s working in mice,” he adds. “Then, let’s have a cup of coffee.”

So far, IS110 family members do not seem to work well in mammalian cells, says Hiroshi Nishimasu, a structural biologist at the University of Tokyo who worked with Hsu to determine the mechanism by which an IS110 enzyme targets DNA. The team is now trying to engineer them to work better in the mammalian cells.

Still in the early stages, but it sounds like it has potential.