Table 1 Hypothetical case studies
Case Example 1 Introduction of a novel substance to inhibit Plasmodium falciparum infection and development A novel gene has been introduced to the mosquito genome using the CRISPR/Cas9 system which encodes a protein that inhibits maturation of Plasmodium ookinetes. The CRISPR/Cas9 system enables the introduced construct to serve as a template for homology directed recombination, resulting in preferential inheritance of the transgenes by the majority of mosquito progeny. This modification is not primarily intended to alter the behaviour, life cycle or population dynamics of the mosquito, although it may impose some fitness cost (i.e., quantitative reduction in survival or reproduction), but it blocks the successful completion of the malaria parasite life cycle in these mosquitoes, rendering them less likely to transmit the disease to humans. |
Case Example 2 Gene editing of a native gene to inhibit Plasmodium falciparum infection A CRISPR/Cas9 gene drive has been engineered for insertion at a site that disrupts proper expression and translation of a gene encoding a cell surface receptor protein that is expressed in the An. gambiae midgut. This receptor is required for completion of the P. falciparum lifecycle. Although the endogenous function of the receptor is not fully understood, mosquitoes harbouring the mutation show only a modest impact on fitness, but are substantially less able to transmit the disease to humans. |
Case Example 3 Gene editing to affect the sex ratio Sex determination in An. gambiae makes use of sex-specific chromosomes, where an XX genotype produces a female phenotype and an XY genotype produces a male phenotype. Thus, the sex of the offspring is determined by the chromosome contributed paternally and under natural conditions where the sex ratio is approximately 50/50 male to female. A ‘knock-in’ gene editing construct has been used to insert a novel gene into the An. gambiae genome. This novel gene is activated during spermatogenesis and triggers cell death in spermatocytes containing an X chromosome. As a result, male carriers of the gene drive can only sire male offspring. The resulting decrease in the number of females is expected to suppress the population. |
Case Example 4 Gene editing to reduce female fecundity A CRISPR/Cas9 gene drive has been engineered to insert at a site that disrupts expression of a protein transporter that is necessary for proper egg provisioning (the transport of materials into developing oocytes from specialized somatic cells). As a result, females carrying the gene drive have greatly reduced fecundity. Males are unaffected and the mating of carrier males with wild-type females is expected to lead to population suppression. |