Biologists: Let’s sic ‘gene drive’ on Zika-carrying mosquitoes

A small group of biologists is itching to use a revolutionary new genetic technique to quell the outbreak of Zika. They believe they could wipe out the mosquitoes spreading the Zika virus within a couple of years, but they need money to do the work — fast.

The scientists in California and Massachusetts say the still-experimental technique, called gene drive, could eliminate local populations of the Aedes aegypti mosquitoes that are spreading Zika in South and Central American and the Caribbean. This approach would simultaneously stop the spread of dengue fever and other diseases the same insects transmit when they bite people.

“Quite a few people are trying to develop a gene drive for population suppression of Aedes,” said biologist Anthony James of the University of California, Irvine, a pioneer in genetic techniques of mosquito control. Last year, he led a team that used gene drive to create mosquitoes that have an immune system that blocks transmission of the malaria-causing parasite and which transmit that genetic trait to essentially all of their descendants. If the technique works in the field, it could wipe out a disease-carrying population of mosquitoes within months.

That is the key advantage of gene drive over existing genetic techniques for mosquito control. British biotech company Oxitec has developed male mosquitoes that are genetically engineered to produce only nonviable offspring once they leave the cushy confines of the lab. Any female that makes her once-per-lifetime mating with an Oxitec male produces no descendants. The company is awaiting approval from federal regulators to release millions of sterile males in the Florida Keys to reduce Aedes populations as a way of combating dengue fever and has conducted field tests in Brazil, Panama, and the Cayman Islands, reducing Aedes populations by some 90 percent.

Gene drives have the potential to change the genetic makeup of entire populations, like mosquitos that carry Zika virus.Hyacinth Empinado/STAT

Gene drive offers a way to eliminate an Aedes population more quickly and cheaply, using and releasing fewer lab-engineered mosquitoes than Oxitec’s approach, which requires batches of insects to be released repeatedly, James and his colleagues reported last year. In a gene drive system, a trait genetically engineered into a few individuals spreads rapidly through a population, as those individuals transmit the gene to all their descendants rather than only some. Last year two teams of biologists, James’s in California and one in London, reported that they had used gene drive in mosquitoes that carry malaria, with the London team producing sterile insects.

“If we were funded, we could do it now and have it ready in less than a year,” said James, referring to a gene drive targeting Aedes populations. “It then would have to go through the field trials, but at least we would be working on something with a good chance of helping.”

Massachusetts Institute of Technology biologist Kevin Esvelt, a pioneer of gene drive, said “international collaborations to hit [Aedes] are already in the works.” The plan, he said, is to build gene drives “spreading resistance to all of the viruses” that Aedes carries. “Zika has been added to the list.”

Unlike with chemicals used to control mosquitoes, Esvelt said, it will be “very hard for viruses to evolve resistance” to gene drive. “We should have this covered in a few years if people agree it should be done.”

Are you at risk for contracting Zika virus? Your level of risk depends in part on your living conditions.Alex Hogan/STAT

Because Aedes often carry not only Zika but also dengue (and sometimes yellow fever), James said the smart play is not to engineer a gene drive that makes the mosquito immune system attack the virus, as he and his colleagues did for malaria, but to engineer one that makes insects sterile. “It doesn’t make sense to build a mosquito resistant to Zika if it could still transmit dengue,” James said. “You want to go for population suppression.”

No more than half a dozen labs in the world have the ability to transform Aedes using gene drive, he said. “But at this point there has been no effort” to get emergency funding to them as part of the world’s Zika response.

“It would be nice if there were some kind of support outside of the standard” funding route, which for academics in the United States means the National Institutes of Health, James said. It can take a year or more to win NIH funding.

The federal government’s main conduit for research on public health emergencies, the Office of the Assistant Secretary for Preparedness and Response, and its Biomedical Advanced Research and Development Authority (BARDA), can quickly write eight-figure checks to fund R&D, as it did during the recent Ebola outbreak. BARDA, however, “has authority to do work on medical countermeasures, but not vector control measures,” said spokesman Bill Hall.

It is not clear if any other federal agency wants to or can step up to support gene-drive research targeting Zika. The World Health Organization does not fund lab research like this; the Gates Foundation, which supports research on mosquito control as part of its malaria work, did not respond to a question about whether it might support studies on using gene drive to stop Zika.