April 21, 2011

Genetic Breakthrough Could Help Control Malaria

Scientists have developed a method of genetically manipulating large populations of mosquitoes, which could one day be used to significantly reduce the spread of the deadly malaria parasite to humans.

The researchers found that after making specific genetic changes to a few mosquitoes, and then letting them breed, these genetic alterations could be spread through large mosquito populations in just a few generations.

The system, known as a gene drive mechanism, was published online Wednesday in the journal Nature.

Malaria is a deadly disease that affects more than 300 million people each year, killing 800,000.  Although health experts have called for malaria eradication, there is a need for better and lower cost tools to achieve that goal.  

The researchers from Imperial College London and the University of Washington, Seattle bred mosquitoes with a green fluorescent gene, as a marker that can easily be observed in experiments. They allowed these insects to mate with a small number of mosquitoes that carried a segment of DNA coding for an enzyme capable of permanently inactivating the fluorescent gene.  After each generation, the scientists counted how many mosquitoes still retained an active fluorescent gene.

They found that in experiments that began with close to 99% of green fluorescent mosquitoes, more than half had lost their green marker genes in just 12 generations.

The study is the first successful proof-of-principle of its kind, and suggests the technique could also be used to propagate a genetic change within a wild mosquito population.

"This is an exciting technological development, one which I hope will pave the way for solutions to many global health problems. It demonstrates significant potential to control these disease-carrying mosquitoes. We expect to conduct many more experiments to determine its safety and reliability," said Professor Andrea Crisanti of Imperial College London, a senior author of the study and head of the research group.

In 2000, the scientists at Imperial were the first to genetically modify a mosquito species.  Research by other scientists has since shown that such modifications could be used to generate mosquitoes that are less able to transmit the malaria parasite.

However, even if such mosquitoes were to be released in large numbers, the modification would quickly disappear since it gives the insect no advantage over the unmodified mosquitoes.

The current research addresses this long-standing obstacle.  The researchers inserted a unique segment of DNA that produces a common homing enzyme into the mosquito Anopheles gambiae, one of the main carriers of malaria.

The particular DNA element not only produces the enzyme that inactivates the green fluorescent gene, but also inserts a copy of itself in the place of the inactivated gene.  This occurs in the mosquitoes' sperm cells, so that when the insects mate almost all the offspring receive the DNA that produces the enzyme, allowing the element to spread through the population over successive generations.

"Malaria is still a terrible disease. There are around 3,500 species of mosquito in the world, but only a few of them transmit the deadly malaria parasite, Plasmodium falciparum. This technology allows us to focus exclusively on controlling these most dangerous species," said Professor Austin Burt of Imperial College London, also a senior author on the study.

"In our mosquitoes the homing endonuclease gene is only passed on, through reproduction, 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 lead author Dr. Nikolai Windbichler, also from Imperial College London.

The team is now working on targeting genes that the mosquito needs for reproduction or malaria transmission. Using the new technology, the release of a small number of modified mosquitoes could ultimately result in a dramatic reduction in the numbers of malaria-carrying mosquitoes in areas where the disease is endemic. However, the scientists expect this additional research will take 5-6 years.

On the Net: