FROM: ScienceNOW: Gene Therapy for Mosquitoes
31 March 1998 07:30 PM

Gene Therapy for Mosquitoes

Like flying syringes, mosquitoes excel at pricking your skin and drawing blood. But some species also inadvertently spread diseases, like malaria. Now researchers have taken an important step toward genetically altering mosquitoes so that they are incapable of transmitting disease. A report in the current issue of the Proceedings of the National Academy of Sciences describes a new method to insert genes into a mosquito that get passed on to its offspring.

One obstacle to genetically engineering mosquitoes has been the lack of a clear "marker"--a distinctive genetic trait that can reveal whether a gene was successfully inserted. Biologist Frank Collins of the University of Notre Dame in Indiana realized that the answer was as close as the lab next door, which for 30 years had been maintaining a colony of mutant mosquitoes with white eyes instead of the usual reddish brown. Collins and Anthony James of the University of California, Irvine, thought they might use the mutant bug to test a fancy trick: Take a bit of DNA, called a transposon, that likes to wiggle into genomes, and use it to insert a fruit fly gene for darker eye color into a mosquito's DNA.

The researchers hitched the genes for dark eyes to the transposons as cargo. Then one of the team members painstakingly injected the transposon into 900 white-eyed mosquito embryos--each about the size of a typewritten 'i.' They aimed for the part of the embryo that produces sperm or eggs in the adult. One generation later, they had their proof that the approach works: Of 120 surviving adults, three had offspring with eye colors that were reddish brown instead of white, Collins says.

The work is just the first step on the long road to engineering disease-resistant mosquitoes, says Becky Wattan, a biologist at the University of Arizona. The next step is to home in on the mutation that knocks out disease transmission and rig it to spread through a population.

Tuesday March 31 12:51 PM EST

Mosquito Gene Switch May Help Stop Malaria

NEW YORK (Reuters) -- Manipulating the genes of mosquitoes might someday help prevent the transmission of mosquito-borne illnesses, researchers say.

"From a medical perspective, the major interest is to see if we can identify genes that will interfere with the ability of (the) mosquito to support development of parasites like malaria parasites, or mosquito-borne viruses like dengue and yellow fever," explained Dr. Frank Collins, formerly of the Centers for Disease Control and Prevention (CDC), now at the University of Notre Dame in Notre Dame, Indiana.

Collins, along with colleagues at the CDC and the University of California at Irvine, publish the study findings in the current issue of the Proceedings of the National Academy of Sciences.

Bites from disease-carrying mosquitoes spread illnesses such as malaria and dengue fever, which kill millions of people every year. So far, scientists have not yet discovered an effective vaccine for either malaria or dengue fever.

But in an interview with Reuters, Collins explained that genetic manipulation of the Aedes aegypti mosquito (the species which transmits malaria) might render the insect incapable of transmitting malaria parasites.

In their test case, Collins and his fellow researchers used transposable gene elements to spread genetically-directed changes in eye color through succeeding generations of mosquitoes.

Collins explained that these "transposon" elements "are small DNA sequences that reside in the genomes of most organisms. Sometimes they are referred to as 'jumping genes."'

Transposons are able to detach themselves from one genetic location and insert themselves into another. At the same time, this move necessitates the creation of a copy of the transposon to fill the gap left behind. This means that potentially thousands of copies of this gene can be created in a single individual. "If an individual that is saturated with transposons mates with an individual that does not have transposons, the offspring will all have half the saturation," Collins explained. He says this means that "transposons can effectively propagate in a way that drives them through a population, so that ultimately every member of the population is saturated with transposons."

When the researchers introduced an eye-color gene into A. aegypti mosquito embryos, they discovered that the flies took on the transposon-directed eye color for at least the next 10 generations.

Scientists say that if the technique works with characteristics such as eye color, it should work for genes which hinder the mosquito from harboring the malaria parasite. "The long range goal will be to drive such antiparasite genes into the natural population of mosquitoes," Collins said.

He says any research into a genetic means of thwarting disease transmission does not mean science should abandon its search for a vaccine or cure for mosquito-borne illnesses. Collins believes transposon techniques would not be "an exclusive (disease) control strategy but rather a new method to be used in conjunction with anything else that may be effective or partially effective."

Public health officials blame the resurgence of malaria worldwide on the increasing resistance of mosquitoes to insecticides, and on growing resistance of the malaria parasite to many drugs used to treat the disease.

SOURCE: Proceedings of the National Academy of Sciences (1998-95:3743-3747)

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