Genetically Modified Mosquitoes and Gene Drives: Engineering our Future

If a gene drive is coupled to another gene, both will be passed on together to the progeny. Target Malaria, a group of scientists aiming to use genetic engineering to eliminate malaria, has had success with this coupling. Instead of using an antibiotic gene, Target Malaria focused on using the sex-distorter gene drive that will create a population of mostly male Anopheles mosquitoes. Since only female mosquitoes can bite and infect humans, a population of male mosquitoes will stop the spread of malaria and will eventually die out as fewer and fewer mates will be available.

Lab tests using the sex-distorter gene drive have shown success. In a 2020 study, Target Malaria researchers found that the insertion of this gene drive created a heavily male population, and eventually led to population reduction. The gene used as the gene drive was the doublesex gene, a highly conserved gene, or a gene that does not readily mutate. This is another breakthrough – for gene drives to be successful, the mutation rate needs to be low. Finding a gene drive that doesn’t easily mutate means it is less likely to become resistant to the sex distorter component.

Gene drive technology, however, is far from perfect. One major problem is mutations. Random mutations can and do occur, interfering with the efficacy of the gene drives. Although this issue can be somewhat avoided by using a gene that is highly conserved (such as the doublesex gene), the possibility will always be there. Additionally, ethical concerns abound – if mosquitoes and fruit flies can have their DNA edited, what else can this technology be used for? Scientists try to account for this issue by creating a reversal drive to undo their gene drive if needed, but there are bound to be ramifications from the use of this technology.  

With the existence of insect birth control (Sterile Insect Technique and Incompatible Insect Technique), what advantages do these new genetically modified mosquitoes offer?

• Most forms of insect birth control require large numbers of insects to be continuously released into the environment. Based on current research, genetically modified mosquitoes that are coupled to a gene drive can spread their genes from a low starting frequency. A modest number of these genetically modified mosquitoes can transmit their new genes throughout a large population.
• This new method is potentially even more effective than Wolbachia IIT. When the University of California researchers added antibodies to the Ae. aegypti mosquito DNA, they included a control test of mosquitoes treated with Wolbachia IIT. Mosquitoes that were homozygous (had two copies) for the antibody gene were more effective at stopping the spread of dengue that Wolbachia IIT mosquitoes. Heterozygous mosquitoes that only had one copy of the antibody had the same efficacy as the Wolbachia IIT mosquitoes.

These methods of genetic modification and gene drives have not been tested in the wild. There are still many more stages of testing before these mosquitoes will be viable options, but for now they remain an area of further study and a potential future fix for vector-borne diseases.