New genetic biocontrol to reduce disease-carrying mosquitoes

A photograph of 3 mosquitoes held in a test tube with a hand wearing a blue glove
Aedes aegypti mosquitoes in a test tube. Credit: Bloomberg Creative Photos/Getty Images

Researchers have developed a new pest control method known as the Toxic Male Technique (TMT), which works by genetically engineering male insects to produce venom proteins in their semen. 

Males transfer the insecticidal proteins when they mate with females, significantly reducing the females’ lifespans.

The approach could be used to reduce the threat of disease-carrying insects such as Aedes mosquitoes, which transmit dengue, Zika, chikungunya disease and yellow fever, and Anopheline mosquitoes, which transmit malaria.

Only the females of these species are capable of biting and transmitting disease, but TMT could make it possible to immediately suppress this population.

“As we’ve learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics,” says Sam Beach of Macquarie University in Australia, lead author of the new Nature Communications study describing the technique.

Insect-borne diseases pose a significant threat to human health, causing more than 700,000 deaths each year. This burden is expected to worsen as the warming climate alters the animals’ abundance and distribution.

An overreliance on insecticides has led to the widespread emergence of resistance, so genetic biocontrol approaches are being used as an alternative to reduce populations of disease-spreading species.

Current techniques, including the Sterile Insect Technique (SIT) or insects carrying lethal genes (RIDL), work by releasing massive numbers of sterilised or genetically modified males to mate with wild females.

These females go on to produce no offspring or only male offspring. However, they continue to spread disease until they die naturally, so populations of biting females only decrease in the next generation.

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“By targeting the female mosquitoes themselves rather than their offspring, TMT is the first biocontrol technology that could work as quickly as pesticides without also harming beneficial species,” says Beach.

Experiments in fruit flies (Drosophila melanogaster) showed that the lifespans of females mated with TMT males were shortened by 37–64%, compared to females mated with normal males.

The venom proteins, which originate from the Phoneutria nigriventer spider and the Anemonia sulcata sea anemone, pass through the female reproductive tract and enter the insect’s circulatory system, called the haemolymph, to act on receptors in the central nervous system.

These proteins were specifically chosen to only effect targets in invertebrates (animals without a spine) and aren’t toxic to mammals. They are also unlikely to be harmful if TMT males are eaten by beneficial insects, as their toxicity through oral ingestion is much lower.

The researchers developed a computer model to simulate the use of TMT in an Aedes aeqypti release program and found that TMT may reduce female blood feeding rates by 40–60% compared to leading biocontrol technologies.

“We still need to implement it in mosquitoes and conduct rigorous safety testing to ensure there are no risks to humans or other non-target species,” says study senior author Mciej Maselko of the ARC Centre of Excellence in Synthetic Biology at Macquarie University.

“This innovative solution could transform how we manage pests, offering hope for healthier communities and a more sustainable future,” says Beach.

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