Colorado State University Leads Project to Engineer Virus-Resistant Mosquitoes; Development Could Reduce Incidence of Dengue Fever

A study led by Colorado State University researcher Ken Olson shows that mosquitoes can be genetically engineered to be weapons against infectious diseases. The study, which engineered the insects to be resistant to dengue fever virus, could help protect people from the disease, the most important mosquito-borne viral disease affecting humans in recent years.

Dengue fever infects 100 million people each year, according to the Centers for Disease Control, and has a case-fatality rate of about 5 percent if untreated, primarily among children and young adults. The disease is principally spread by mosquitoes and passed between mosquitoes and people.

Researchers triggered a naturally-occurring anti-viral pathway in the mosquitoes. Triggering the pathway, called RNA interference, allowed the researchers to reduce or prevent the mosquitoes’ ability to transmit the virus. The insects were made resistant to the virus, of which there are four types.

"The research results of this study offer promising results for halting the spread of this disease by disarming mosquito’s ability to contract and transmit the dengue type-2 virus, a cause of dengue fever," said Olson, a researcher in the College of Veterinary Medicine and Biomedical Sciences. "It demonstrates that it’s feasible to develop a mosquito that won’t transmit the disease to people by genetically triggering their RNA interference pathway."

According to the Centers for Disease Control, dengue fever is endemic to about 100 countries including the United States, Cuba, Africa, Columbia, Brazil, Puerto Rico and the Caribbean Islands.

Colorado State University researcher Alexander Franz manipulated the DNA of mosquito embryos by introducing the DNA of a dengue-resistant gene into the embryo. The mosquito was engineered so that it expressed an effector molecule in the mosquito’s gut as the mosquito took in blood containing virus.

This effector molecule turned on the RNA interference pathway in gut cells making the cells inhospitable to dengue virus replication. The resulting mosquitoes were resistant to the virus and also were fertile, which lends hope to researchers that they could be introduced into wild mosquito populations and have a widespread impact on the spread of the disease.

During the study, not all of the genetically engineered mosquitoes showed 100 percent resistance to the virus.

"We could potentially replace wild repopulations of mosquitoes with similarly engineered mosquitoes over time, as the wild populations breed with the resistant strains," Olson said. "For this purpose, the engineered mosquitoes would need to reach 100 percent resistance to the virus."

The control technique could be applied to other vector-borne diseases such as malaria.

A vaccine for dengue virus is not available. Dengue hemorrhagic fever is the most severe form of dengue and it can be fatal if it is not properly treated. Symptoms of dengue include high fever, severe  headache, backache, joint pains, nausea and vomiting, eye pain and rash. Younger children generally exhibit milder symptoms than older children and adults. Dengue hemorrhagic fever lasts from two to seven days with nausea, vomiting, abdominal pain and headache, followed by symptoms such as easy bruising, skin hemorrhages, bleeding nose or gums and possibly internal bleeding. There are no specific medications for treating dengue or dengue hemorrhagic fever, but the conditions can be treated if they are recognized.

This research, supported by the National Institutes of Health, was performed in collaboration with researchers at the University of California-Irvine.