title: Feasible introgression of an anti-pathogen transgene into an urban mosquito population without using gene-drive.
abstract: BACKGROUND
  Introgressing anti-pathogen constructs into wild vector populations could reduce disease transmission. It is generally assumed that such introgression would require linking an anti-pathogen gene with a selfish genetic element or similar technologies. Yet none of the proposed transgenic anti-pathogen gene-drive mechanisms are likely to be implemented as public health measures in the near future. Thus, much attention now focuses instead on transgenic strategies aimed at mosquito population suppression, an approach generally perceived to be practical. By contrast, aiming to replace vector competent mosquito populations with vector incompetent populations by releasing mosquitoes carrying a single anti-pathogen gene without a gene-drive mechanism is widely considered impractical.
  
  
  RESULTS
  Here we use Skeeter Buster, a previously published stochastic, spatially explicit model of Aedes aegypti to investigate whether a number of approaches for releasing mosquitoes with only an anti-pathogen construct would be efficient and effective in the tropical city of Iquitos, Peru. To assess the performance of such releases using realistic release numbers, we compare the transient and long-term effects of this strategy with two other genetic control strategies that have been developed in Ae. aegypti: release of a strain with female-specific lethality, and a strain with both female-specific lethality and an anti-pathogen gene. We find that releasing mosquitoes carrying only an anti-pathogen construct can substantially decrease vector competence of a natural population, even at release ratios well below that required for the two currently feasible alternatives that rely on population reduction. Finally, although current genetic control strategies based on population reduction are compromised by immigration of wild-type mosquitoes, releasing mosquitoes carrying only an anti-pathogen gene is considerably more robust to such immigration.
  
  
  CONCLUSIONS
  Contrary to the widely held view that transgenic control programs aimed at population replacement require linking an anti-pathogen gene to selfish genetic elements, we find releasing mosquitoes in numbers much smaller than those considered necessary for transgenic population reduction can result in comparatively rapid and robust population replacement. In light of this non-intuitive result, directing efforts to improve rearing capacity and logistical support for implementing releases, and reducing the fitness costs of existing recombinant technologies, may provide a viable, alternative route to introgressing anti-pathogen transgenes under field conditions.
authors.affiliation: Department of Entomology, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Kenichi W
authors.initials: KW
authors.lastname: Okamoto
authors.affiliation: Department of Mathematics and Biomathematics Graduate Program, North Carolina State University, Raleigh, North Carolina, United States of America; Department of Biology and the Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Robert
authors.affiliation: Department of Entomology, North Carolina State University, Raleigh, North Carolina, United States of America; Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Fred
authors.initials: F
authors.lastname: Gould
authors.affiliation: Department of Mathematics and Biomathematics Graduate Program, North Carolina State University, Raleigh, North Carolina, United States of America; Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Alun L
authors.initials: AL
authors.lastname: Lloyd
mesh_terms: D000330:Aedes / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D003140:Communicable Disease Control / Q000379:methods*; D007303:Insect Vectors / Q000235:genetics*; D009032:Mosquito Control / Q000379:methods*; D010568:Peru; D019076:Transgenes / Q000235:genetics*