Self-deleting genes promise risk-free genetic engineering of mosquitoes

They might be small and their kills may be indirect, but for humans, mosquitoes are the deadliest animals on the planet by quite a margin. While tackling the diseases these annoying insects spread is one approach to reduce their lethality, others are looking to attack the problem at the bloodsucking source through genetic engineering. A new project by Texas A&M AgriLife Research is looking to enable "test runs" of genetic changes to mosquitoes that are automatically deleted.

Various angles of attack using genetic engineering to combat mosquitoes have been pursued in recent years, including modifying them so they pass on infertility, don't grow wings, can't spread malaria or have impaired smell. But making genetic modifications to an organism and then releasing them into the wild runs the risk of unintended and harmful consequences that may be difficult to reverse.

That's where the new Texas A&M AgriLife Research project comes in. It is looking to enable "test runs" of genetic modifications that would then automatically be deleted from the mosquitoes' genetic code after a period of time.

“People are wary of transgenes spreading in the environment in an uncontrolled manner," says Zach Adelman, Ph.D, a principal investigator on the project. "We feel that ours is a strategy to potentially prevent that from happening. The idea is, can we program a transgene to remove itself? Then, the gene won’t persist in the environment."

The researchers have evaluated three potential ways to achieve such self-deletion and chosen to focus on one that leverages a process used by all animals to repair damaged DNA. The proposal is to introduce a "gene drive" – a genetic component designed to force the spread of modified genes in a population – along with a DNA-cutting enzyme and a small repeat of the mosquitoes' own DNA.

Because repair enzymes inside cell nuclei look for repeated genetic sequences around broken DNA strands and delete what's between the repeated sequences, the hypothesis is that when the introduced enzyme cuts the DNA, the mosquitoes' own repair tools will delete the gene drive genes, along with the other added sequences.

The researchers have already started work to examine different gene drives and ascertain how long they persist in flies and mosquitoes. The goal is to have a gene drive spread through the lab population quickly, before the introduced genes disappear after a few generations and the population has reverted to wild-type individuals. Such a process then would then allow different genetic engineering strategies to be trialed without the risk of undesirable modifications persisting in the wild.

The project will receive US$3.9 million in funding from the National Institute of Allergy and Infectious Diseases over the next five years to develop the self-deleting gene technology.

Source: Texas A&M AgriLife