Genetically-engineered mosquitoes lose nose for humans

It has long been believed that detecting carbon dioxide was one of the ways that mosquitoes target their human prey. But the fact that mosquitoes tend to favor certain people over others indicates that some other odor also plays a part in the attraction. Researchers at the Howard Hughes Medical Institute (HHMI) have genetically engineered mosquitoes to alter their sense of smell, which could provide the understanding required to block the pesky pests' attraction to humans.

A team led by Leslie Vosshall altered the odor-sensing capabilities of Aedes aegypti, a mosquito found in tropical and subtropical regions that is a vector for dengue fever, yellow fever and other diseases. Following on from her lab’s previous success in genetically engineering flies to delete a gene called orco, which they knew affected the flies’ ability to respond to odors, Vosshall’s team used zinc-finger nucleases to specifically mutate the orco gene in the mosquito.

After injecting the targeted zinc-finger nucleases into mosquito embryos, the researchers waited for them to mature before identifying the mutant individuals and generating mutant strains that allowed them to study the role the orco gene plays in mosquito biology.

They found that the genetically engineered mosquitoes exhibited a reduction in neural activity related to odor-sensing, with subsequent tests revealing various behavioral changes. Whereas normal Aedes aegypti will make a bee-line (or mosquito line) for humans when given the choice between a human and another animal, the mosquitoes with orco mutations showed a reduced preference for humans over guinea pigs. These results were seen even in the presence of carbon dioxide.

“By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans,” says Vosshall.

However, the researchers still aren’t sure whether this confusion is due to an inability by the engineered mosquitoes to sense a “bad” smell coming from the guinea pig, or a “good” smell coming from the human, or both.

The researchers also found that the mosquitoes with orco mutations responded differently to DEET, the active ingredient in most insect repellents. When presented with two human arms, one covered in a solution containing 10 percent DEET, and the other untreated, the mosquitoes showed no preference for either arm, suggesting that they couldn’t smell the DEET. However, those that landed on the DEET-covered arm quickly flew away.

“This tells us that there are two totally different mechanisms that mosquitoes are using to sense DEET,” explains Vosshall. “One is what’s happening in the air, and the other only comes into action when the mosquito is touching the skin.” The researchers say this dual mechanism had never been identified before.

The research team plans to continue their study of the orco protein and how it interacts with the mosquitoes’ odor receptors.

“We want to know what it is about these mosquitoes that makes them so specialized for humans,” she says. “And if we can also provide insights into how existing repellants are working, then we can start having some ideas about what a next-generation repellant would look like.”

Even though mosquitoes cause more human deaths than any other animal, they do perform some beneficial ecological functions. So finding a more effective insect repellent would likely be a more palatable idea for those opposed to the idea of using genetic engineering to wipe the mosquito out altogether.

Source: HHMI