Zika, malaria, dengue, chikungunya: all of these diseases are transmitted by a simple mosquito bite. Pesticides have always been our champions in controlling insect populations to limit the spread of these diseases. However, they may indiscriminately target other populations, and these effects are becoming more apparent. Ongoing public concern about pesticide use, along with the ability of insects to develop resistance, has prompted the search for alternatives.
Recent developments in molecular biology have made it possible to use the pest's genome against itself, by artificially inducing mutations in specific genes that weaken the population. Endonucleases play an essential role in this genome manipulation. These enzymes drive the cleavage of specific DNA sequences, thus disrupting gene expression and allowing researchers to insert new DNA coding for traits that weaken the population. New developments in the application of the CRISPR-Cas9 endonuclease system have simplified the process of cutting DNA sequences to inactivate or mutate genes. This approach allows researchers to convert an embryo that has two identical copies of a gene into an embryo that has a normal copy of the gene and a second, mutated copy that can be passed on to subsequent generations.
Andrew Hammond and colleagues decided to use this approach in a bid to control the population of Anopheles gambiae, the mosquito that transmits malaria, by creating a mutation in a gene essential for fertility. Females with two mutated genes will be sterile, while those with one copy of the mutated gene will be fertile. Usually, this type of mutation would be removed from the population, but the authors used a novel technique called ‘gene drive’, which ensures that the DNA alteration persists, allowing the mutation to be passed to future generations. This novel method of pest control would yield sterile mosquitos in every generation, therefore decreasing the overall number of individuals in the population.
Identifying three genes that result in reduced fertility – two that may play roles in gamete and embryo development, and a third with a possible role in mosquito larval molting – the team was able to mutate all three using the CRISPR-Cas9 system and verify that the mutations could be passed on to the insects’ offspring with an 87.3–99.3% success rate. This confirmed that gene disruptions driven by the CRISPR-Cas9 system can be propagated in the population, thus allowing DNA alterations to occur in multiple mosquito generations. Using laboratory experiments and a model to predict whether the mutations would spread if released into the population, the team showed that a mutation in the third gene would spread in the wild mosquito population and reduce their numbers, while the mutations in the other two genes would disappear over time.
The study by Hammond and colleagues is one of a few to break ground in a new era of mosquito population control. They have shown that the CRISPR-Cas9 system effectively disrupts gene expression associated with fertility and have identified a potential target gene for controlling the A. gambiae population. With no release of chemicals into the environment, no effects on non-target populations and a smaller chance of resistance developing, genome editing in the mosquito population could prove to be a beacon of hope for a malaria-free future.
