A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs

Abstract

A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.