Self-propagating CRISPR gene drives have been shown to work in controlled populations of fruit flies, mosquitoes and yeast. Gene drives can be “self-propagating” or “self-exhausting”: the former are designed so that they can always spread as long as there are wild organisms around, whereas the latter are expected to lose their ability to spread over time. In this way, for example, a gene that prevents mosquitoes from carrying or transmitting the malaria parasite could be introduced to a very large wild population to reduce the incidence of the disease among humans. This is because components of the CRISPR system can be tailored to replace alternative copies of a particular gene, ensuring that only the desired version is passed on to offspring.

Among the types of gene drive systems, those based on the CRISPR genome editing technology are predicted to be able to spread genes particularly rapidly. Gene drive is a genetic engineering technology that can spread a particular suite of genes throughout a population. Our mathematical results suggest that self-propagating gene drive is best suited to applications such as malaria prevention that seek to affect all wild populations of the target species. Hence, initiating contained field trials as tentatively endorsed by the National Academies report on gene drive could potentially result in unintended spread to additional populations. Releasing a small number of organisms will often cause invasion of the local population, followed by invasion of additional populations connected by very low rates of gene flow.

Our models show that although resistance prevents spread to fixation in large populations, even the least effective drive systems reported to date are likely to be highly invasive. Here we develop mathematical models based on existing empirical data to explicitly test this assumption for population alteration drives. Recent reports have suggested that self-propagating CRISPR-based gene drive systems are unlikely to efficiently invade wild populations due to drive-resistant alleles that prevent cutting.

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