Self-eliminating genes tested in mosquitoes
Texas A&M AgriLife Research scientists have tested a technology to make temporary genetic changes to mosquitoes. Changes clear themselves over time.
The mechanism for making temporary genetic changes could be important for scientists hoping to modify mosquitoes in ways that help manage populations and prevent vector-borne diseases like West Nile virus without permanently altering composition. genetics of wild populations.
An article detailing their test results, “Designing a self-eliminating transgene in the yellow fever mosquito, Aedes aegyptiwas published in Proceedings of the National Academy of Sciences‘PNAS Nexus. Writers, Zach Adelmandoctorate and Kevin MylesPh.D., both professors at Texas A&M College of Agriculture and Life Sciences Department of entomologydescribe a method to program the deletion of modified genes in mosquito populations over several generations.
The method is a first step towards building safeguards for genetic modifications developed to control mosquito populations and the vector-borne diseases they carry. The idea is to test the proposed changes without making them permanent and without risking passing them on to wild populations, Adelman said.
“There are a lot of green questions that we don’t know the answers to, and when you’re testing technology, you don’t want to find yourself in a situation where you have to tell a regulatory agency or the public that ‘if something bad happens, we’re just unlucky,” Adelman said. “This mechanism is about how we get back to normal, whether or not the experience goes as planned.”
Adelman and Myles co-lead a team of scientists who received a five-year, $3.9 million grant from the National Institute of Allergy and Infectious Diseases to test and refine the self-eliminating transgene technology.
Back to normal in a few generations
To prevent mosquito-borne diseases, approaches based on genetic control of insect populations are being developed, Adelman said. However, many of these strategies are based on highly invasive, self-propagating transgenes that can rapidly spread the trait to other mosquito populations.
Keun Chae, Ph.D., a postdoctoral researcher in Adelman’s group, led the experiments on Aedes aegypti mosquitoes, which are known disease vectors. Taking advantage of a form of DNA repair, Chae engineered a duplicate region of genetic code as well as two genes for fluorescent proteins in the middle of an important gene for eye pigment.
The result was a white-eyed mosquito, as well as red and green fluorescence in the eyes and body. When combined with a site-specific nuclease, which is essential for many aspects of DNA repair, they act as a precise set of molecular scissors that can cut transgene sequences. Over several generations, the mosquitoes regained their normal eye pigment and lost the altered genes.
Adelman said the work is proof of principle that scientists can do two important things: delete transgenes placed in mosquitoes and repair disrupted genes.
“Many groups are developing genetic methods for controlling mosquito populations,” Adelman said. “Our method provides a braking system capable of restoring sequences in nature.”
Self-editing transgenes could be a leap forward for genetic research
Myles said creating this self-editing transgene is the first step in a longer process. The mosquito genome is not easy to manipulate and this breakthrough is the culmination of approximately six years of experimental work.
But this first publication is beginning to address concerns about genetic modification in wild populations, he said. As genetic modification technology advances, Adelman and Myles believe this mechanism will allow researchers to more safely assess the effects of changes in the environment and on animals other than mosquitoes.
“These are highly conserved genetic pathways, and there is every reason to believe that this method could be applied to a wide range of organisms,” Myles said.
The two scientists are eager to extend the application of their discovery in the context of a highly active gene drive. They hope their method will be useful to geneticists and push the boundaries of genetic research.