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Binary Expression Drives

Among several potential uses, (CRISPR) gene drives can be designed to suppress, and eventually eliminate, a target population. Designs of most such drives are intended to disrupt an essential gene for viability or fertility. To spread, these drives require the disrupted alleles to be largely recessive and preferentially affect only females, i.e. the target gene should be both haplosufficient for females and, for the best outcome, nonessential for males. If the drive carried a dominant lethal gene, which may avoid the need of targeting endogenous genes, it would impose too high of a fitness penalty and, consequently, it would not be able to invade the population.

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This restriction, however, may be sorted by using simultaneously two different gene drives to spread a split binary expression system. One drive would carry a dominant lethal effector alone and the other a transcriptional activator (transactivator factor). As in any binary expression system, the effector would only be expressed in the presence of the transactivator factor. Such a system may be advantageous as the reduced fitness costs would allow each drive to rapidly spread from rare. Only after reaching sufficiently high frequencies, would individuals have the chance to inherit both system components and the effector be expressed, killing or sterilizing them. Then, the population may be suppressed.

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Interestingly, this concept could be implemented to spread engineered seminal proteins designed to kill females. Males carrying both (the driver and the effector) drives would behave as "terminators" of females, transferring into them lethal toxins. In polyandrous species, where females mate with several males, this intervention could be very fast and efficient (see our mathematical modeling article).

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