Mosquito research

File photo of Indians meeting with a nurse as they wait for consultations in the out-patient wing of the Government Gandhi Hospital in Secunderabad, the twin city of Hyderabad, on Sept. 6, 2019, as patients flooded hospitals in Telangana with cases of dengue fever. The work of U.C. San Diego professor Omar Akbari’s lab shows “it is possible to immunize mosquitoes and prevent their ability to transmit dengue virus, and potentially other mosquito-borne pathogens,” said Suresh Subramani, Indian American professor emeritus of molecular biology at U.C. San Diego. (Noah Seelam/AFP via Getty Images)

An international team of scientists, led by a team from U.C. San Diego associate professor Omar Akbari’s lab, has synthetically engineered mosquitoes that halt the transmission of the dengue virus.

The university reports that the research team describes details of the achievement in Aedes aegypti mosquitoes, the insects that spread dengue in humans, in the journal PLOS Pathogens, which was published Jan. 16.

Researchers in Akbari’s lab worked with colleagues at Vanderbilt University Medical Center in identifying a broad-spectrum human antibody for dengue suppression.

The development marks the first engineered approach in mosquitoes that targets the four known types of dengue, improving upon previous designs that addressed single strains, the report said.

They then designed the antibody “cargo” to be synthetically expressed in female A. aegypti mosquitoes, which spread the dengue virus, it said.

“Once the female mosquito takes in blood, the antibody is activated and expressed—that’s the trigger,” Akbari, of the Division of Biological Sciences and a member of the Tata Institute for Genetics and Society, said in the report.

“The antibody is able to hinder the replication of the virus and prevent its dissemination throughout the mosquito, which then prevents its transmission to humans. It’s a powerful approach,” he adds.

Akbari said the engineered mosquitoes could easily be paired with a dissemination system, such as a gene drive based on CRISPR/CAS-9 technology, capable of spreading the antibody throughout wild disease-transmitting mosquito populations, according to the report.

According to the World Health Organization, dengue virus threatens millions of people in tropical and sub-tropical climates. Severe dengue is a leading cause of serious illness and death among children in many Asian and Latin American countries.

The Pan American Health Organization recently reported the highest number of dengue cases ever recorded in the Americas, the report adds.

Infecting those with compromised immune systems, dengue victims suffer flu-like symptoms, including severe fevers and rashes. Serious cases can include life-threatening bleeding. Currently no specific treatment exists and thus prevention and control depend on measures that stop the spread of the virus.

“This development means that in the foreseeable future there may be viable genetic approaches to controlling dengue virus in the field, which could limit human suffering and mortality,” said Akbari, whose lab is now in the early stages of testing methods to simultaneously neutralize mosquitoes against dengue and a suite of other viruses such as Zika, yellow fever and chikungunya, according to the U.C. report.

“Mosquitoes have been given the bad rap of being the deadliest killers on the planet because they are the messengers that transmit diseases like malaria, dengue, chikungunya, Zika and yellow fever that collectively put 6.5 billion people at risk globally,” said Suresh Subramani, Indian American professor emeritus of molecular biology at U.C. San Diego and global director of the Tata Institute for Genetics and Society.

“Until recently, the world has focused on shooting (killing) this messenger. Work from the Akbari lab and at TIGS is aimed at disarming the mosquito instead by preventing it from transmitting diseases, without killing the messenger,” Subramani adds. “This paper shows that it is possible to immunize mosquitoes and prevent their ability to transmit dengue virus, and potentially other mosquito-borne pathogens.”

Funding for the research was provided by a Defense Advanced Research Project Agency Safe Genes Program Grant, a National Institutes of Health Exploratory/Developmental Research Grant Award and CSIRO internal funding.

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