Researchers at Imperial College in London have for the first time managed to use a revolutionary new gene editing technique to eliminate an entire population of malaria-carrying mosquitos in the laboratory.
The “gene drive” has been heralded for several years as a potential way to control pests in the environment, and has been touted as an option for eliminating invasive species on islands, as well as controlling Lyme disease and other threats.
The gene drive approach works by overriding the normal Mendelian rules of genetic inheritance, where an organism inherits half its genes from each parent. In gene drives, a modified gene is transmitted to offspring 100 percent of the time.
However, past research has suffered from the drawback that target organisms have been able to halt the gene drive through mutations that restore the function of the targeted gene, which is then selected for over multiple generations. The Imperial researchers saw no mutations, however, raising hopes that their approach might be a relatively “resistance-proof” way of targeting malaria.
In 2016 there were 445,000 deaths from malaria — 90 percent of them in sub-Saharan Africa. Malaria control efforts using bed-nets and insecticides have been fairly successful in reducing transmission, but the mosquitos are now evolving resistance to many insecticides, reducing their effectiveness.
The gene drive approach holds promise because it is entirely targeted at a single species of mosquito, Anopheles Gambiae, which transmits the malaria parasite. Although there are hundreds of types of mosquito, only a few bite humans and transmit disease.
Writing in the journal Nature Biotechnology, the research team reported that it had been able to crash the population of A. Gambiae in cages by 100 percent over seven to 11 generations by introducing the gene drive element on modified mosquitos.
Lead researcher Professor Andrea Crisanti of the Department of Life Sciences at Imperial said: “This breakthrough shows that gene drive can work, providing hope in the fight against a disease that has plagued mankind for centuries. There is still more work to be done, both in terms of testing the technology in larger lab-based studies and working with affected countries to assess the feasibility of such an intervention.
“It will still be at least five to 10 years before we consider testing any mosquitoes with gene drive in the wild,” she continued, “but now we have some encouraging proof that we’re on the right path. Gene drive solutions have the potential one day to expedite malaria eradication by overcoming the barriers of logistics in resource-poor countries.”
The team targeted a gene in An. gambiae called “doublesex,” which determines whether an individual mosquito develops as a male or as a female. Females with two copies of the modified gene showed both male and female characteristics, failed to bite and did not lay eggs.
By the end of the experiment, all the mosquitos in the cages ended up either male or female intersex, and the population crashed as the insects failed to reproduce.
If released in the wild, the hope is that this gene drive might one day be able to eliminate malaria over large areas of Africa, saving hundreds of thousands of lives per year.
Some critics have raised fears that a gene drive targeting malarial mosquitos would be irreversibly altering the ecosystem. However, separate research by a different team at Imperial found that A. Gambiae has no predators that entirely depend on it, and its elimination would likely have little effect on the wider ecosystem.
The next step for the Imperial College London team will be to test the gene drive approach in more realistic confined laboratory environments that better mimic conditions in tropical countries and with larger populations of mosquitos.
The researchers concluded their paper on a hopeful note by pointing out that the doublesexgene they had targeted occurs in all known insect species. This “suggests that these sequences might be an Achilles heel present in many insect pests that could be targeted with gene editing approaches.”