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Genetically-engineered mosquitoes find humans less attractive

Researchers have genetically engineered mosquitoes to alter the way they respond to odors and block the insects’ attraction to humans.

In 2007, scientists announced the completion of the full genome sequence of Aedes aegypti, the mosquito that transmits dengue and yellow fever. This new research, led by Leslie Vosshall, an investigator at the Rockefeller University, focused on genetically engineering the insects to understand why the insect is so attracted to humans, and how to block that attraction.

Photo credit: João Trindade
Photo credit: João Trindade

Vosshall’s first target: a gene called orco, which her lab had deleted in genetically engineered flies 10 years earlier. The researchers knew this gene was important for flies to be able to respond to odors and believed that the orco gene might serve a similar function in mosquitoes.

Vosshall’s team turned to a genetic engineering tool called zinc-finger nucleases to specifically mutate the orco gene in Aedes aegypti. They injected the targeted zinc-finger nucleases into mosquito embryos, waited for them to mature, identified mutant individuals, and generated mutant strains that allowed them to study the role of orco in mosquito biology. The engineered mosquitoes showed diminished activity in neurons linked to odor-sensing. Then, behavioral tests revealed more changes.

When given a choice between a human and any other animal, normal Aedes aegypti will reliably buzz toward the human. But the mosquitoes with orco mutations showed reduced preference for the smell of humans over guinea pigs, even in the presence of carbon dioxide, which is thought to help mosquitoes respond to human scent. Vosshall said:

A female Aedes aegypti mosquito feeding on the arm of HHMI investigator Leslie Vosshall.
A female Aedes aegypti mosquito feeding on the arm of HHMI investigator Leslie Vosshall. Photo credit: Zach Veilleux (The Rockefeller University)

By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans,

Next, the team tested whether the mosquitoes with orco mutations responded differently to DEET. When exposed to two human arms—one slathered in a solution containing 10 percent DEET, the active ingredient in many bug repellants, and the other untreated—the mosquitoes flew equally toward both arms, suggesting they couldn’t smell the DEET. But once they landed on the arms, they quickly flew away from the DEET-covered one. Vosshall explained:

This tells us that there are two totally different mechanisms that mosquitoes are using to sense DEET. One is what’s happening in the air, and the other only comes into action when the mosquito is touching the skin.

Vosshall and her collaborators next want to study in more detail how the orco protein interacts with the mosquitoes’ odorant receptors to allow the insects to sense smells. She said:

We want to know what it is about these mosquitoes that makes them so specialized for humans. 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.

The new research was published May 29, 2013 in the journal Nature.

Bottom line: New research, published May 29, 2013 in the journal Nature, focused on genetically engineering mosquitos to understand why the insect is so attracted to humans, and how to block that attraction.

Read more from Howard Hughes Medical Institute

May 30, 2013

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