Heritable strategies for controlling insect vectors of disease

Abstract

Mosquito-borne diseases are causing a substantial burden of mortality, morbidity and economic loss in many parts of the world, despite current control efforts, and new complementary approaches to controlling these diseases are needed. One promising class of new interventions under development involves the heritable modification of the mosquito by insertion of novel genes into the nucleus or of Wolbachia endosymbionts into the cytoplasm. Once released into a target population, these modifications can act to reduce one or more components of the mosquito population's vectorial capacity (e.g. the number of female mosquitoes, their longevity or their ability to support development and transmission of the pathogen). Some of the modifications under development are designed to be self-limiting, in that they will tend to disappear over time in the absence of recurrent releases (and hence are similar to the sterile insect technique, SIT), whereas other modifications are designed to be self-sustaining, spreading through populations even after releases stop (and hence are similar to traditional biological control). Several successful field trials have now been performed with Aedes mosquitoes, and such trials are helping to define the appropriate developmental pathway for this new class of intervention.

Keywords: RIDL; Wolbachia; dengue; homing endonuclease genes; malaria; population genetic engineering.

Figure 1.

The logic of alternative gene drive systems. (a) Cytoplasmic incompatibility as induced by maternally transmitted Wolbachia bacteria. Infected females (W⁺) have an advantage because they can mate successfully with all males, whereas uninfected females (W^–) can only mate successfully with uninfected males—matings with infected males produce few or no offspring. (b) Y chromosome drive, such as could be caused by an enzyme that cleaves the X chromosome at male meiosis, results in the majority of functional sperm bearing the Y chromosome, and a predominance of males among the progeny. (c) Homing endonuclease genes (H) cause the homologous chromosome to be cut and then get copied across during the repair process, converting a heterozygote into a homozygote. If the homing endonuclease gene is inserted into a host gene, then its spread through the population can lead to a population-wide gene knockout. (d) MEDEA elements gain a relative advantage because embryos from heterozygous (M⁺/M^–) mothers die if they did not inherit the element (i.e. are homozygous M^–/M^–).