May 2, 2011

Selfish Genes Could Block Malaria Transmission

Close-up photo of a mosquito on skin An Anopheles gambiae mosquito feeding. James Gathany, CDC.

Scientists have developed a way to spread genetic modifications to large numbers of mosquitoes. The new “gene drive” technique may represent a major step forward in the fight against malaria.

Malaria is an infection that affects the red blood cells and liver. Although it’s treatable and has been eradicated in the United States, malaria remains a serious problem in developing countries. It kills hundreds of thousands worldwide every year. A single-celled parasite called Plasmodium is responsible for the illness. The most deadly variety is transmitted to people through the bite of a mosquito called Anopheles gambiae.

Because mosquitoes transmit the malaria parasite, blocking transmission from insects to humans is potentially as useful as attacking the parasite itself. Scientists are currently able to genetically modify mosquitoes to diminish their ability to spread disease. However, they haven’t yet found a way to effectively spread these modifications from laboratory mosquitoes to a larger population in the wild.

Scientists from the Imperial College of London and the University of Washington Seattle teamed up to solve this problem. Led by senior authors Drs. Austin Burt and Andrea Crisanti, they used a genetic drive strategy to spread a genetic modification among a mosquito population. Their study was partially funded by NIH’s National Institute of General Medical Sciences (NIGMS) and National Cancer Institute (NCI), as well as the Foundation for the National Institutes of Health. The results were published in the advance online edition of Nature on April 20, 2011.

The team used a special type of gene called a homing endonuclease gene (HEG), which is found only in single-celled organisms. HEGs are so-called selfish genes, which promote their own survival. HEGs make proteins that cleave DNA at a specific place. As the cell mends the broken DNA strands, a copy of the HEG is inserted at the repair site. The team believed that this property could be used to inactivate genes in the mosquitoes and pass these changes on to the insects’ offspring.

To test their theory, the team made mosquitoes with a gene for a fluorescent protein that made the insects glow green. The gene included a sequence targeted by the HEG. The researchers also produced mosquitoes that expressed HEG in their sperm cells. If the system worked, the mosquitoes’ offspring would cease to glow as the selfish genes spread and disrupted the fluorescent protein genes.

The technique worked. In cages with 10% of the insects carrying the gene drive system, less than half of the mosquitoes still glowed after 12 generations. Genetic analysis confirmed that the loss of fluorescence was due to the insertion of the HEG.

In further experiments, the researchers showed they could design HEGs to recognize other mosquito sequences. These results now open the possibility for using HEGs to control wild-type mosquito populations.

"This is an exciting technological development, one which I hope will pave the way for solutions to many global health problems,” Crisanti says. “It demonstrates significant potential to control these disease-carrying mosquitoes. We expect to conduct many more experiments to determine its safety and reliability.”

— by Allison Bierly, Ph.D.

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