Scientists manipulate mosquitoes in malaria fight

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Scientists working on malaria have found a way of genetically manipulating large populations of mosquitoes that could eventually dramatically reduce the spread of the deadly disease.

In a study in the journal Nature, researchers from Imperial College London and the University of Washington, Seattle found that after making specific genetic changes to a few mosquitoes and then allowing them to breed on, genetic alterations could be spread through large mosquito populations in a few generations.

This is the first successful proof-of-principle experiment of its kind, they said, and suggests the method may in future be used to spread genetic changes in wild mosquito populations to make them less able to transmit malaria.

"This is an exciting technological development, one which I hope will pave the way for solutions to many global health problems,” said Andrea Crisanti of Imperial’s life sciences department, who led the study.

Malaria is an infectious disease that affects more than 240 million people every year, and kills around 850,000 annually—many of them children in Africa.

Health experts have called for malaria eradication and genetic ways of manipulating or eradicating mosquitoes have been suggested as possible alternatives to existing control methods such as pesticides and bednets. But the success of a genetic approach depends on getting the genetic modification to spread effectively in large mosquito populations.

‘GENETIC DRIVE’

In these new experiments, the scientists showed that a modified genetic element—a homing endonuclease gene called I-SceI—can efficiently spread through caged populations of mosquitoes. The genetic element ‘homes’ to a particular portion of the DNA, they explained, where it becomes integrated into the broken chromosome.

This process—known as genetic drive—could be used to transmit a genetic change through a population of mosquitoes that affects the insects’ ability to carry malaria.

Crisanti’s team bred mosquitoes with a green fluorescent gene as a marker that can easily be spotted in experiments. They allowed these insects to mate with a small number of mosquitoes that carried a segment of DNA coding for an enzyme which can permanently inactivate the fluorescent gene. After each generation, they counted how many still had a green gene.

The results showed that after starting with almost 99 percent of fluorescent mosquitoes, more than half had lost their green genes in just 12 generations.

There are around 3,500 species of mosquito in the world, but only a few transmit the malaria parasite, Plasmodium falciparum. The researchers said this technique should allow scientists to focus on controlling just the most dangerous species.

“In our mosquitoes the homing endonuclease gene is only passed on… directly to the carrier’s offspring. This makes for a uniquely safe biological control measure that will not affect even very closely related mosquito species,” said Imperial’s Nikolai Windbichler, who also worked on the study.

The team is now working on targeting genes that the mosquito needs for reproduction or malaria transmission. With this technology, the release of a few modified mosquitoes could eventually cause a dramatic reduction in malaria-carrying mosquitoes in countries where the disease is endemic, they said.

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By Kate Kelland, Health and Science Correspondent

LONDON

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