Summer barbecues have a special place in my heart. The smell of charcoal-grilled burgers. Ice-cold fizzy drinks. Music, laughs—and the incessant buzzing of mosquitoes.
While mostly a nuisance at backyard parties, the blood-sucking critters carry a range of potentially life-threatening diseases, such as dengue fever, malaria, and encephalitis. Malaria alone causes roughly half a million deaths each year, mostly in developing countries.
Mosquito nets help reduce transmission. But a more permanent solution would be to block the disease from passing between mosquitoes and humans altogether. The malaria parasite replicates in the mosquito gut and infects people through the bug’s saliva. Get rid of the mosquito middleman, and we may nip malaria and other blood-borne diseases in the bud.
Gene drives are one way to do this. These engineered genetic chunks override the rules of inheritance to push a gene down an entire family line. In one example, scientists engineered mosquitoes that, when they bred with their natural counterparts, gave rise to offspring that couldn’t reproduce. In limited lab tests, the gene drives eventually wiped out the population.
Not everyone is on board with erasing an entire species. Mosquitoes may stabilize ecosystems in ways we don’t yet appreciate.
Alternatively, we could “vaccinate” mosquitoes against malaria. In a new study, researchers did just that. The team found a protective version of a protein that naturally occurs in some types of mosquitoes. Using a gene drive, they spread the gene coding for the protein through a population of the bloodsuckers in the lab.
When fed human blood contaminated with malaria, the engineered mosquitoes and their offspring thwarted the parasite.
“This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts,” wrote the team from the University of California, San Diego, and other institutions.
Weighted Coin
Inheritance is a coin toss. Offspring have a roughly 50 percent chance of inheriting a gene from either parent.
Gene drives break that rule. Over the past decade, scientists have engineered snippets of DNA that pass down generations with extremely high probability. From weeds and insects to mammals, the method rapidly pushes a gene through multiple generations of an entire species and irreversibly changes their genetic makeup.
Researchers are exploring how gene drives might wipe out unwelcomed plants, make mouse models for research, and tackle invasive rodents. But gene drives are perhaps most intriguing in efforts to fight mosquito-transmitted diseases, including malaria. An estimated 597,000 people, mostly young children, died of the disease in 2023. Although there are malaria vaccines, another way to tackle the disease is to lower the number of mosquitoes carrying it.
In one study, scientists edited a gene that controls sexual development in mosquitoes. They genetically encoded Cas9—the “molecular scissors” that snip DNA in CRISPR gene editing—into one mosquito family and an RNA “bloodhound”—the molecule that guides Cas9 to its target—into another line. When the two lines mated, the now complete gene editor mutatedthe gene and killed off all female mosquito larvae, leaving only males—which don’t bite humans. It was only a matter of time, then, before there weren’t any females left, marking the end of the species.
While eradicating these annoying bloodsucking disease vessels sounds like a good plan, there’s room for thought. Bioethicists and ecologists are hotly debating the potential unforeseen consequences of driving mosquitoes to extinction.
Alternatively, we might make them uninhabitable to the parasites. In one study, for example, researchers engineered mosquitoes to produce antibodies that thwart malaria parasites. But for the method to make an impact, the gene has to spread across an entire population, with the edited mosquitoes healthy enough to compete against their natural counterparts.
The Protective Gene
The new study turned a naturally occurring protein in mosquitoes into a weapon.
Called FREP1, the protein is essential for malaria parasites to infect a mosquito’s gut. Previous studies discovered that some mosquitoes of the species Anopheles gambiae, often found in Africa, harbor a mutated form of the protein that blocks malaria from replicating.
The team first added the protective variant to A. stephensi, the major mosquito carrier of malaria in Asia. The mutants were similar to their natural counterparts in body size, lifespan, and reproduction. When pitted against controls in an enclosed cage, where each bug fought for food and mates, the mutants held their own. Ten generations later, the ratio of mosquitoes carrying the protective gene remained the same, suggesting the edit is “fitness neutral.”
But the mutants have a leg up: When fed human blood contaminated with the malaria parasite P. falciparum, the edited mosquitoes had only a 30 percent infection rate compared to 80 percent in controls. The infected mutants showed far lower amounts of the parasite in their guts—a “striking decrease,” wrote the team—and nearly none in their salivary glands, which are the main source of transmission. In other words, even infected mosquitoes might not be able to pass the parasite on to humans.
The protective gene also made the mosquitoes resistant to another type of malaria parasite seen in rodents, suggesting it could potentially tackle multiple strains at once.
So far, all of the mutant mosquitoes were born with the traditional 50-50 chance of carrying the protective gene. To speed up its spread, the team engineered the mutated FREP1 into a gene drive using CRISPR-Cas9 and delivered it to normal mosquitoes.
The bugs produced both components of the gene editor in their reproductive cells, where the Cas9 “scissors” snipped the standard FREP1 gene. As cells repaired the DNA breakage they swapped in the malaria-resistant version. The edited mosquitoes could now pass the protective variant—the only version of the gene remaining—to their offspring, making them resilient to malaria infection. In 10 generations, prevalence of the protective gene skyrocketed from 25 percent to more than 94 percent in the studied population.
The technology is promising but isn’t ready for a field test. The gene drive doesn’t cause extinction, but it could produce unintended consequences in the wild. For example, malaria parasites might evolve resistance to the mutated gene, stripping the mosquitoes—and us—of protection.
The team is now tinkering with alternative strategies. One idea is to convert gene variants that make mosquitoes resistant to insecticides into “sensitive” variants that die with a light spray. Another is to add a self-eliminating mechanism into the gene drive, so it only acts temporarily before disappearing from the population. This could allow more fine-tuned control in a species without lasting consequences.
For now, we’ll just have to keep donning mosquito repellant and swatting the pesky bugs in the backyard.
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