Genetic engineering of animals, plants and microorganisms has been a mainstay technique in biomedical science and comparative medicine for decades and has greatly increased our knowledge of disease-states and basic biological function. Recent discoveries and breakthroughs in genetic engineering, including zinc finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced palindromic repeats (CRISPR), have made it easier and faster than ever to produce powerful genetic models. The potential for this technology extends beyond biomedical research and into the biotechnology sector where researchers are already seeking applications for engineering pest-resistant crops and drug-producing yeast.

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However, as gene editing technologies have grown faster and easier to use, so too have concerns about potential unintended consequences. 'Gene drive systems' that use CRISPR and the associated Cas9 endonuclease enable edited genes to be inherited and passed along through a population at exponential rates that are much higher than those of typical Mendelian inheritance. While this can be beneficial, for instance when changing a malfunctioning gene that is associated with a specific disease, if an off-target gene is accidentally altered and then spread through a population, it could have harmful and permanent consequences.

To address these issues, James DiCarlo and colleagues at the Wyss Institute for Biologically Inspired Engineering at Harvard University (Cambridge, MA), developed an experimental paradigm with the CRISPR-Cas9 gene drive system that minimizes the risk of synthetic genes escaping into wild populations (Nat. Biotechnol. 33 1250–1255; 2015). Typically, gene drive systems based on CRISPR-Cas9 are self-sufficient, with all the components built-in that are necessary for targeting and driving a specific gene. DiCarlo et al. split the drive system into two separate components: the Cas9 endonuclease, which physically cuts targeted genes, and the guide RNA that is necessary to drive the inheritance of the edited gene. This split-drive system ensures that even if genetically altered yeast were to escape from the lab, mating with wild-type yeast would quickly separate Cas9 from the RNA drive, greatly slowing the spread of altered genes through the wild population and minimizing their impact. “The gene drive research community has been actively discussing what should be done to safeguard shared ecosystems, and now we have demonstrated that the proposed safeguards work extremely well and should therefore be used by every gene drive researcher in every relevant lab organism”, commented Kevin Esvelt, a senior author of the study, in a press release.