‘e-Drive’: New gene drive reverses insecticide resistance in pests, then disappears

Pesticides have been used for centuries to combat widespread pest damage to valuable food crops. Eventually, over time, beetles, moths, flies, and other insects develop genetic mutations that make the insecticides less effective.

Increasing resistance from these mutants is forcing farmers and vector control professionals to increase the frequency and concentration of toxic compounds, making it difficult for most pesticides to kill ecologically important insects and pests. It kills both, posing a risk to human health and damage to the environment.

To address these issues, researchers have recently developed a powerful technique to genetically remove mutated insecticide-resistant genes and replace them with genes that are more susceptible to insecticides. These gene drive technologies, based on CRISPR gene editing, have the potential to protect valuable crops and significantly reduce the amount of chemical pesticides needed to control pests.

Still, gene drive systems have come under intense scrutiny due to concerns that once released into a population, they can continue to spread unchecked.

Geneticists at the University of California, San Diego have developed a solution to this concern. Postdoctoral researcher Ankush Auradkar and Professor Ethan Beer from the School of Biological Sciences, published in Nature Communications, have created a new genetic system that returns a mutated insect gene to a pesticide-resistant form back to its native form. led. This new system exploits the biased inheritance of certain genetic variants, known as alleles, to spread the original “wild-type” version of the gene, which then dies out, allowing insects to carry the modified version of the gene. It is designed to leave only the population of

“We have developed an efficient biological approach to reverse insecticide resistance without causing any other disruption to the environment,” said Professor Bier of the Department of Cell and Developmental Biology. In other words, he talked about “e-Drive.” “e-drives are programmed to work temporarily and then disappear from people.”

As described in the paper, the researchers created new genetic “cassettes” – small groups of DNA elements – and inserted them into the bodies of fruit flies as a proof-of-concept technique that could be applied to other insects. They developed an e-Drive that targets a gene known as voltage-gated sodium ion channel (vgsc), which is required for proper nervous system function.

The e-Drive cassette is designed to be spread through CRISPR gene editing and includes a guide RNA that binds to the Cas9 DNA protein and cuts the targeted vgsc insecticide resistance gene site. That gene is then switched to a native copy of the gene that is more susceptible to pesticides.

Studies have shown that when insects equipped with the cassette are introduced into a target population, they mate randomly and transmit the e-Drive cassette to their offspring. To keep the spread of e-drives under control, researchers subjected those in possession of the cassettes to fitness tests with limited viability or fertility. This cassette was inserted into the X chromosome, reducing male mating success and producing fewer offspring. The frequency of the cassette in the population eventually decreases with each generation and eventually disappears from the population completely.

In laboratory experiments, all offspring were converted to the native gene in eight to 10 generations, a process that took about six months in flies.

“Insects carrying the gene cassette are subject to severe adaptation costs, so the element is rapidly eliminated from the population and only lasts long enough for 100 percent of the insecticide-resistant target gene to revert to wild type.” said Auradkar.

The researchers note that e-Drive’s self-removal nature means it can be introduced and reintroduced as needed and when different types of pesticides are used. Researchers are currently developing a similar e-Drive system for mosquitoes to prevent the spread of malaria.

Co-authors of the Nature Communications paper include Auradkar and Bier, as well as their close collaborator Rodrigo Corder of the Institute of Biomedical Sciences at the University of São Paulo. John Marshall of the Institute for Innovative Genomics performed sophisticated mathematical modeling to uncover important hidden aspects of e-drive systems, including the ability to efficiently cull classes of individuals in which the drive process did not occur. Characteristics revealed.