Designing gene drives to limit spillover to non-target populations

G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim,  PLOS Genetics,  17:e1009278. 2021.

CRISPR-based gene drive is an emerging genetic engineering technology that enables engineered genetic variants, which are usually designed to be harmful to the organism carrying them, to be spread rapidly in populations. Although this technology is promising for controlling disease vectors and invasive species, there is a considerable risk that the gene drive could unintentionally spillover from the target population, where it was deployed, to other non-target populations. We develop mathematical models of gene-drive dynamics that incorporate migration between a target and non-target populations to investigate the possibility of effectively applying a gene drive in the target population while limiting its spillovers to the non-target population (‘differential targeting’). We observe that the feasibility of differential targeting depends on the gene-drive design specification, as well as on the migration rates between the populations. Even when differential targeting is possible, as migration increases, the possibility for differential targeting disappears. We find that differential targeting can be effective for low migration rates, and that it is sensitive to the design of the gene drive under high migration rates. We suggest that differential targeting could be used, in combination with other mitigation measures, as an additional safeguard to limit gene drive spillovers.


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