Gene Drive Strategies for Population Replacement

Introduction

After 3.8 billion years of research and development, Nature has provided inspiration for a plethora of human design problems. During the Renaissance, Leonardo da Vinci designed a flying machine inspired by the anatomy of birds. Today, Nature’s evolutionary solutions are inform- ing the design of solar panels from photosynthesis, and digital displays using the light-refracting properties of butterfly wings. Nature’s intricate structures and processes may also help in the fight against mosquito-borne diseases. Gene drive—the process whereby natural mechanisms for spreading genes into populations are used to drive desirable genes into populations (e.g., genes conferring refractoriness to malaria or dengue fever in mosquitoes)— is another example of Nature’s processes being applied for the benefit of humanity. Gene drive systems may either spread from low initial frequencies or display threshold properties such that they are likely to spread if released above a certain frequency in the population and are otherwise likely to be eliminated. Population replacement, in this context, refers to the process whereby a population of disease-transmitting mosquitoes is replaced with a population of disease-refractory ones. Several approaches are being explored to engineer mosquitoes unable to transmit human diseases, and there have been a number of notable successes. For example, Isaacs et al. have engineered Anopheles stephensi mosquitoes expressing single-chain antibodies that prevent Plasmodium falciparum malaria parasites from developing in the mosquito, thus preventing onward transmission of the parasite. Gene drive systems are expected to be instrumental in spreading disease-refractory genes into wild mosquito populations, given the wide geographical areas that these spe- cies inhabit and the expectation that refractory genes will be associated with at least modest fitness costs. Gene drive systems are also being considered to implement population suppression strategies whereby genes conferring a fitness load or gender bias are instead driven into the vector population, thereby reducing disease transmission.

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