Developing Disease-free Mosquitoes

By Susan Trulove

A decade ago, scientists announced their ability to introduce foreign genes into the mosquito genome. A year ago, scientists announced the successful use of an artificial gene that prevented a virus from replicating within mosquitoes. But how does one apply what can be done with a small number of mosquitoes in a lab to the tens of millions of mosquitoes that spread disease worldwide?

Researchers at Virginia Tech and the University of California Irvine have demonstrated that they can cause a foreign gene to express itself exclusively in the female mosquito germline, a necessary prerequisite to future genetic control strategies in mosquitoes where all progeny of lab and wild mosquitoes will have the gene that blocks virus replication – or whatever trait has been introduced into the lab mosquitoes.

Until now, if lab-grown mosquitoes that are unable to support virus replication were to mate with wild, disease-vector mosquitoes, only half of their offspring would have the antivirus gene. Researchers have been working on how to skew the outcome so that all offspring lack the ability to spread disease. However, these experiments have been hampered by the inability to express foreign genes in the mosquito germ cells.

“We needed to gain access to the cells in the reproductive germline to change the way traits are inherited,” says Zach Adelman, assistant professor of entomology and a member of the Vector Borne Infectious Disease Research Group at Virginia Tech.

Working with Aedes aegypti, the mosquito that carries yellow fever and dengue fever viruses, the researchers are working to create a “genedrive system” by using instructions copied from the nanos (nos) gene, which is essential for germline formation. “Think of the nanos instructions as a key to a room,” says Adelman.

Using the nanos “key,” the researcher team successfully achieved germline-specific expression of Mos1, an enzyme isolated from the housefly that is a transposable element (TE) – a piece of genetic material that moves around. Mos1 can also move anything attached to it and can duplicate itself and whatever is attached to it, such as a gene that directs the denguevirus to stop replication.

The research shows that the scientists can access the female germline and can perform experiments in the germline. “The nanos control sequences show promise as a part of a TE-based gene drive system,” says Adelman.

Although this discovery brings researchers a step closer to developing disease resistant mosquitoes, Adelman stresses
there is much more to learn.

“We need to understand the basic immune system of the mosquito and how it interacts with viruses,” says Adelman. “Not knowing how this interaction works makes us helpless to predict what will happen when we change something.”

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Yellow Fever Mosquito
Genetic transformation of the yellow fever mosquito, Aedes aegypti. This female expresses a fluorescent protein in her eyes, as a signal that genetic information has been successfully added to her chromosomes.

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