US and British researchers have genetically engineered a strain of flightless mosquito that may help curb the spread of Dengue fever, a flulike disease that is endemic to over 100 countries and affects tens of millions of people every year.

The researchers, from the University of California, Irvine (UCI) in the US, the University of Oxford and Oxitec Limited in the UK, wrote about their work in a paper published online on 22 February in the Proceedings of the National Academy of Sciences, PNAS.

Dengue fever, which can cause mild to severe symptoms, is one of the world’s most pressing public health problems. There are up to 100 million cases worldwide every year, and according to the World Health Organization (WHO), one in five people in the world, or 2.5 billion people, are now at risk from Dengue fever.

The Dengue virus is spread through the bite of infected female Aedes aegypti mosquito and there is no vaccine or treatment.

Co-author Dr Anthony James, an internationally recognized vector biologist and distinguished Professor of microbiology and molecular genetics and molecular biology and biochemistry at UCI, told the media that:

“Current Dengue control methods are not sufficiently effective, and new ones are urgently needed.”

“Controlling the mosquito that transmits this virus could significantly reduce human morbidity and mortality,” he added.

The researchers anticipate that flightless Aedes aegypti females will die quickly in the wild, thus cutting down the number of mosquitoes, reducing spread of Dengue and eventually even eliminating it.

Using methods designed by senior author Dr Luke Alphey of Oxitec based on technology he developed when he was at Oxford University, the researchers genetically engineered the Aedes aegypti so that wing muscles don’t develop properly in female offspring rendering them unable to fly.

The idea is to introduce genetically altered males into the wild, they mate with wild females and the females of the next generation are rendered flightless. Males do not inherit the defect: they can fly as normal and show no ill effects from carrying the gene, said the researchers, but when they mate with females they pass on the gene.

The researchers wrote in their paper that they engineered “transgenic strains” of Aedes aegypti to have a “repressible female-specific flightless phenotype using either two separate transgenes or a single transgene, based on the use of a female-specific indirect flight muscle promoter from the Aedes aegypti Actin-4 gene”.

“The technology is completely species-specific, as the released males will mate only with females of the same species,” Alphey told the press.

The researchers estimated that if released, the new breed could sustainably suppress the wild mosquito population in six to nine months: “the strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy”, they wrote.

Alphey suggested that this approach is:

“Far more targeted and environmentally friendly than approaches dependent upon the use of chemical spray insecticides, which leave toxic residue.”

“Another attractive feature of this method is that it’s egalitarian: all people in the treated areas are equally protected, regardless of their wealth, power or education,” he added.

The study is part of a research program sponsored by the Foundation for the National Institutes of Health through the Gates Foundation Grand Challanges for Global Health Initiative, which aims to support breakthrough advances for health challenges in the developing world.

James and Alphey are pioneers in the field of genetically altering mosquitoes to limit spread of disease. They hope that the approach they have developed for Dengue fever could be adapted to control other species of disease-spreading mosquito, including those that spread malaria and West Nile Virus.

“Female-specific flightless phenotype for mosquito control.”
Guoliang Fu, Rosemary S. Lees, Derric Nimmo, Diane Aw, Li Jin, Pam Gray, Thomas U. Berendonk, Helen White-Cooper, Sarah Scaife, Hoang Kim Phuc, Osvaldo Marinotti, Nijole Jasinskiene, Anthony A. James, and Luke Alphey.
PNAS, published online before print February 22, 2010.

Sources: UC Irvine, Oxitec.

Related article: What Is Dengue Fever? What Causes Dengue Fever?

Written by: Catharine Paddock, PhD