E-Insight

April 2006

MIP Group Leads Project to Engineer Dengue Virus-Resistant Mosquitoes

A study led by Colorado State University researcher Dr. 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. Researchers triggered a naturally-occurring anti-viral pathway in the mosquitoes to reduce or prevent the mosquitoes' ability to transmit the virus. This research, supported by the National Institutes of Health, was performed in collaboration with a scientific team at the University of California-Irvine.

"The outcomes of this study offer promising results for halting the spread of this disease by disarming a mosquito's ability to contract and transmit the dengue type-2 virus, a cause of dengue fever," said Dr. Olson, a Professor in the Department of Microbiology, Immunology and Pathology. "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 infects 100 million people annually 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. Dengue fever is endemic to about 100 countries including the United States, Cuba, Columbia, Brazil, Puerto Rico; and countries in the Caribbean islands and on the African continent.

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 mosquitoes were engineered so that they expressed an effector molecule in the gut as they took in blood containing the 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, giving credence to the theory that they could be introduced into wild mosquito populations and have a widespread impact on the spread of the disease. However, during the study, not all of the genetically engineered mosquitoes showed 100 percent resistance to the virus.

"We could potentially replace wild populations 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."

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. There are no specific medications for treating dengue or dengue hemorrhagic fever, but the conditions can be treated if they are recognized.