What makes a gene drive specific for the targeted species?

Genetic biocontrol strategies can be very species-specific. Much of this specificity rests on the species-specific mating behavior and interspecific sterility observed widely in nature. Gene drive systems depend on production of viable and fertile offspring to be passed on and thus their spreading effect requires productive mating. Genetic engineering methods can be used to enhance target species specificity at multiple levels.

However, sometimes closely related species can and do successfully interbreed. Under such circumstances, additional measures would need to be taken to enhance specificity only for the target species if that is considered necessary. These measures could include constructing the system using components that only function in the target species.

1. All engineered gene drives are assemblages of genes and associated regulatory elements needed for the gene drive system to function in the right cells, at the right time, and in the target organism. Because of the very strict temporal and spatial gene expression requirements for functional gene drives, the regulatory elements used to control gene expression are usually highly species specific.
2. Engineered gene drive constructs using a Cas enzyme from a CRISPR/Cas system include a “guide” component that recognizes a specific sequence in the DNA of the target species and can be chosen by the researcher for its species uniqueness.
3. In addition to the Cas enzyme acting on the correct sequence, the hundreds of bases of DNA flanking the site on the chromosome cut by Cas also need to be sufficiently specific to the intended target gene in order to achieve ‘drive’.