Genomic engineering is a staple of modern translational research; the ability to create alterations at the DNA level and explore their effects in various organisms has deepened our understanding of basic biologic function and of many human health disorders. About a year ago, scientists developed a new approach to genomic engineering called the CRISPR/Cas9 system (Science 337, 816–821; 2012). The system has since been used to engineer many biological model species, including yeast, zebrafish, mice and nematodes. Now, a trio of collaborators from the University of Wisconsin–Madison reports the successful application of this approach in fruit flies (Genetics 194, 1029–1035; 2013). Their results highlight the precision of the CRISPR/Cas9 system and show that genetic alterations made using the system are transmitted to the next generation of flies. Such precision and transmissibility are essential properties in genomic engineering.

In the CRISPR/Cas9 system, the enzyme Cas9 is directed to snip a cell's DNA at a target sequence, stimulating the cell's DNA repair machinery to fill in the break and integrate a genetic alteration of interest. The alteration can be as specific as changing a single base pair in the DNA sequence. The system uses short RNA sequences to direct DNA clipping by Cas9, whereas other genome editing approaches use proteins to direct DNA breaks. The use of short RNAs confers several advantages: they can be generated relatively rapidly, whereas generation of proteins is time-consuming and costly. Moreover, they enable broad applicability of the engineering approach across species.

Kate O'Connor-Giles, who led the fruit fly study along with Melissa Harrison and Jill Wildonger, explained in a press release, “This is so readily transferable that it's highly likely to enable gene knockout and other genome modifications in any organism. It's going to turn non-model organisms into genetic model organisms.”

Wildonger described how applying the CRISPR/Cas9 system in fruit flies can result in clinical benefits. “It can be very difficult and time-consuming to generate models to study all the gene variants associated with human diseases,” she said. “With this genome editing approach, if we work in collaboration with a clinician to find mutations, we can rapidly translate these into a fruit fly model to see what's happening at the cellular and molecular level.”

The broad applicability and fine control offered by the CRISPR/Cas9 approach promise new insights into the fundamental workings of biological systems as well as the mechanisms underlying human disease.