"The time has come now to do genetics in these important disease-vector insects. I think our new work is a great example that you can do it," said Leslie Vosshall, an Howard Hughes Medical Institute (HHMI) researcher, who led the study.
Vosshall's first target: a gene called orco, which her lab had deleted in genetically engineered flies 10 years earlier.
"We knew this gene was important for flies to be able to respond to the odours they respond to. And we had some hints that mosquitoes interact with smells in their environment, so it was a good bet that something would interact with orco in mosquitoes," said Vosshall.
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 odour-sensing. Then, behavioural 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.
"By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans," says Vosshall. Scientists don't know yet whether the confusion stems from an inability to sense a "bad" smell coming from the guinea pig, a "good" smell from the human, or both. The team tested whether the mosquitoes with orco mutations responded differently to insect repellent DEET.
When exposed to two human arms - one slathered in a solution containing 10 per cent DEET, the active ingredient in many bug repellents, and the other untreated - the mosquitoes flew equally toward both arms, suggesting they couldn't smell the DEET.
The study was published in the journal Nature.