James Gallagher BBC News 20 Apr 11;
Scientists believe they are closer to being able to change the DNA of wild mosquitoes in order to combat malaria.
In the laboratory, they made a gene spread from a handful of mosquitoes to most of the population in just a few generations, according to a report in Nature.
If the right gene can be made to spread then researchers hope to reduce the number of cases of malaria.
Other academics have described the study as a "major step forward".
The World Health Organisation estimated that malaria caused nearly one million deaths in 2008.
Spreading resistance
Research groups have already created "malaria-resistant mosquitoes" using techniques such as introducing genes to disrupt the malaria parasite's development.
The research, however, has a great challenge - getting those genes to spread from the genetically-modified mosquitoes to the vast number of wild insects across the globe.
Unless the gene gives the mosquito an advantage, the gene will likely disappear.
Scientists at Imperial College London and the University of Washington, in Seattle, believe they have found a solution.
They inserted a gene into the mosquito DNA which is very good at looking after its own interests - a homing endonuclease called I-SceI.
The gene makes an enzyme which cuts the DNA in two. The cell's repair machinery then uses the gene as a template when repairing the cut.
As a result the homing endonuclease gene is copied.
It does this in such a way that all the sperm produced by a male mosquito carry the gene.
So all its offspring have the gene. The process is then repeated so the offspring's offspring have the gene and so on.
In the laboratory experiments, the gene was spread to half the caged mosquitoes in 12 generations.
Defeating malaria
Professor Andrea Crisanti, from the department of life sciences at Imperial College London, said: "This is an exciting technological development, one which I hope will pave the way for solutions to many global health problems.
"At the beginning I was really quite sceptical and thought it probably would not work, but the results are so encouraging that I'm starting to change my mind."
He said the idea had been proved in principle and was now working on getting other genes to spread in the same way.
He believes it could be possible to introduce genes which will make the mosquito target animals rather than humans, stop the parasite from multiplying in the insect or produce all male offspring which do not transmit malaria.
Professor Janet Hemingway, from the Liverpool School of Tropical Medicine, said the work was an "exciting breakthrough".
She cautioned that the technique was still some way off being used against wild mosquitoes and there were social issues around the acceptability of using GM technology.
"This is however a major step forward providing technology that may be used in a cost effective format to drive beneficial genes through mosquito populations from relatively small releases," she added.
Dr Yeya Touré, from the World Health Organisation, said: "This research finding is very important for driving a foreign gene in a mosquito population. However, given that it has been demonstrated in a laboratory cage model, there is the need to conduct further studies before it could be used as a genetic control strategy."
Scientists Manipulate Mosquitoes In Malaria Fight
Kate Kelland PlanetArk 21 Apr 11;
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.
(Editing by Gareth Jones)
