Scientists have developed a process for implanting the human antibody for dengue fever into mosquitos, potentially limiting their ability to pass the disease on to people.
Researchers led by molecular biologist Omar Akbari of the University of California-San Diego (UCSD) have reengineered an anti-dengue antibody, simplifying the gene’s structure in order to insert it more easily into the genome of the dengue-carrying Aedes aegypti mosquito.
Once the modified mosquitoes mate, their offspring carry copies of the modified gene.
According to the researchers’ article in the January 16 edition of PLOS Pathogens, after the engineered mosquitoes ingested blood with any of the four dengue types, the insects’ saliva exhibited no detectable trace of the virus.
“Results demonstrate that conditional expression of the anti-DENV 1C19 scFv renders mosquitoes refractory to all four major DENV serotypes and therefore appears to be a potent viral inhibition strategy,” the report stated.
Akbari’s team built on the discovery by researchers at Vanderbilt University in 2013 of an antibody, in the blood of a patient who had been infected with the virus multiple times, that strongly bound to all four dengue serotypes and prevented them from infecting new cells.
Multiple Lines of Attack
Dengue fever is a painful, debilitating, mosquito-borne disease caused by any one of four closely related viruses. Dengue affects as many as 400 million people each year in tropical regions.
Efforts to prevent the spread of the disease have included draining of stagnant pools of water in which the insects breed, the use of pesticides, and the installation of protective netting around beds. These efforts have largely proven unsuccessful in stemming the spread of the disease.
Health authorities and researchers have also tried releasing mosquitoes infected with the Wolbachia pipientis bacterium, which blocks viral replication and thus reduces the insect’s ability to spread the virus, but results have been mixed. Not all mosquitoes exposed to the bacterium are rendered unable to spread the disease. The best results thus far reported in studies conducted by the nonprofit World Mosquito Program found a maximum 76 percent reduction in the rate of dengue in some treated locations.
A potential drawback of the UCSD researchers’ modification is that although these genetically engineered mosquitoes mate and produce healthy offspring in the lab, the offspring develop slightly slower than typical mosquitoes, and the females have slightly shorter lifespans, leading to uncertainty as to how well the engineered mosquitoes will be able to compete with their unmodified counterparts in the wild.
Genetically modifying insects to prevent the spread of disease is a promising approach, says Gregory Conko, a senior fellow at the Competitive Enterprise Institute.
“Some releases of modified insects are hugely successful, some are only partially successful, and some don’t work well at all,” Conko said. “But the fact that a particular method or process of pest control isn’t always successful doesn’t mean we should never experiment with it.
“Because this particular effort is intended to target all four known variants of the dengue virus, there is reason to be optimistic, but the proof will be in the pudding,” Conko said. “We just won’t know until it’s tested.”
Another potential problem is that a genetically modified antibody could spark resistance in viruses, says Conko.
“Some viruses are known to have developed resistance to human antibodies, with the influenza virus being a good example of this, so one question that will have to be studied carefully is whether exposure to human dengue antibodies in the genetically engineered mosquitoes could lead to resistance to those antibodies among the wild dengue virus,” Conko said.
“If the wild virus develops resistance, it could make dengue more difficult to combat,” Conko said.
Wild Release Uncertain
Akbari and his team are considering making additional modifications to increase the likelihood of the anti-dengue gene being passed from parent to offspring. They say they hope eventually to be able to release the modified mosquitoes into the wild.
There are potential government obstacles to be surmounted. The pace of approval for genetically modified organisms is slow, and despite the possible lifesaving benefits of genetically modifying mosquitoes to prevent the spread of debilitating diseases such as dengue fever and malaria, authorities, fearing the potential unanticipated consequences of permanently altering the genome of an entire population of mosquitoes, have thus far never approved even a limited release into the wild of mosquitoes genetically modified to pass on disease-fighting traits.
Kevin Stone ([email protected]) writes from Dallas, Texas