Researchers Genetically Modify First Batch Of Mosquitoes Resistant To All Four Types Of Dengue

UC San Diego researchers and their colleagues developed a human antibody in Aedes aegypti mosquitoes, which spread dengue virus. Erik Jepsen, Creative Services and Publications, UC San Diego

An international team of researchers have synthetically engineered a breed of mosquitos that are resistant to all four types of the dengue virus for the first time, a feat they say may someday suppress the disease and stop its transmission to humans.

More than half of the world’s population is at risk of the mosquito-borne viral disease endemic to over 100 tropical and sub-tropical countries around the world. Its flu-like symptoms can be severe, resulting in potentially fatal bleeding and organ shutdown. The Centers for Disease Control and Prevention estimates that every year 400 million people globally become infected with dengue, yet currently there is no treatment for the disease, according to the World Health Organization.

By providing precise modifications to the mosquito genome, researchers believe they can stop the virus’ spread. To do so, researchers from the University of California, San Diego, and Vanderbilt University Medical Center identified a broad-spectrum human antibody from the human immune system that suppresses dengue and neutralizes the virus. Female Aedes aegypti mosquitoes injected with this single-chain variable fragment (scFV) saw significantly reduced viral infection, dissemination, and transmission rates for all four virus serotypes.

Dengue-resistant mosquitoes were given a red-eye gene to distinguish them from regular mosquitoes. CSIRO

"Once the female mosquito takes in blood, the antibody is activated and expressed – that's the trigger," said Omar Akbari, of the Division of Biological Sciences and a member of the Tata Institute for Genetics and Society, in a statement. "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."

Through dissemination systems like a gene drive based on CRISPR/CAS-9 technology, the researchers say it may be possible to create mosquitoes less likely to acquire and transmit deadly viruses, opening up a “new field of biotechnology possibilities." In essence, the practice doesn’t “kill the messenger” but rather prevents the message from being delivered in the first place.

This is the first time an engineering attempt has targeted all four known types of dengue, improving on previous designs that only took aim at single strains. The technology may one day be used to combat other dangerous illnesses such as malaria and yellow fever. Researchers last year reported a way to delete a gene in mosquitos that makes them an excellent malarial host and synthetically made the insects feel full and thus less blood-thirsty. Other work has targeted mosquito eggs or genetically modified individuals so that their offspring is nonviable.

"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 testing methods to neutralize dengue and other viruses like Zika and yellow fever. The study is published in the journal PLOS Pathogens

A team led by Omar Akbari's lab at UC San Diego has engineered the first mosquitoes that repel the four known times of dengue virus. Erik Jepsen, Creative Services and Publications, UC San Diego

 

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