Geneticists have come up with a groundbreaking solution to combat the prevalent issue of insecticide resistance among pests. They have designed an ‘e-Drive’ that not only reverses insecticide resistance but also eventually vanishes from the insect population, ensuring sustainability in pest control.
Insecticides have been a key defense strategy against pest damage to important food crops for centuries. However, over time, various insects like beetles, moths, and flies evolve genetic mutations that make these insecticides ineffective.
The growing resistance of these mutated insects compels farmers and pest control experts to increase their use of harmful chemicals, which poses serious health risks to humans and threatens environmental balance, as many insecticides indiscriminately kill both beneficial insects and pests.
To address these challenges, researchers have recently created advanced technologies that can eliminate insecticide-resistant genes and replace them with genes that are sensitive to insecticides. These gene-drive methods, driven by CRISPR gene editing, have the potential to safeguard valuable crops and significantly cut down on the chemical pesticides needed to control pest populations.
However, gene-drive systems have garnered criticism due to concerns that they could proliferate uncontrollably once introduced into a natural population.
To tackle this issue, geneticists at the University of California San Diego have developed a solution. In a publication in Nature Communications, Postdoctoral Scholar Ankush Auradkar and Professor Ethan Bier introduced a new genetic system that converts mutated insect genes, which make them resistant to insecticides, back to their original, natural state. This innovative system is designed to propagate the native “wild type” version of the gene through a specialized inheritance process and then disappear, leaving behind only insects with the corrected gene.
“We have devised an effective biological method to reverse insecticide resistance without disrupting the surrounding environment,” stated Bier, a professor in the Department of Cell and Developmental Biology, referring to the self-eliminating allelic drive, or “e-Drive.” “The e-Drive is designed to operate temporarily and then exit the population.”
In their study, the researchers created a unique genetic “cassette,” which is a small assembly of DNA components, and tested it using fruit flies to demonstrate its potential for use in other insect species. The e-Drive was engineered to target a gene called the voltage gated sodium ion channel (or vgsc), essential for normal nervous system activity.
The e-Drive cassette employs CRISPR gene editing techniques and includes a guide RNA that interacts with the Cas9 DNA protein to cut at the specific site of the resistant vgsc gene. Subsequently, the gene is replaced with a native version that is susceptible to insecticides.
According to the study, when insects with the cassette are integrated into a target population, they reproduce randomly and pass the e-Drive cassette to their offspring. To manage the e-Drive’s dissemination, the researchers incorporated a fitness penalty on those carrying the cassette, limiting their survival and reproductive success. The cassette was placed on the X-chromosome and significantly decreased the mating success of males, leading to fewer offspring. Over generations, the prevalence of the cassette within the population diminished until it eventually disappeared.
In laboratory trials, all offspring were transformed to possess the native genes within eight to ten generations, which took around six months in fruit flies.
“Due to the substantial fitness cost imposed on insects carrying the genetic cassette, this element is swiftly eradicated from the population, lasting only as long as it takes to revert 100 percent of the insecticide-resistant target gene back to its wild-type form,” Auradkar explained.
The researchers emphasize that the self-eliminating characteristic of the e-Drive allows it to be reintroduced as needed, even as different pesticides are utilized. They are also working on a similar e-Drive system for mosquitoes to aid in the fight against malaria.
In addition to Auradkar and Bier, the co-authors of the Nature Communications paper include Rodrigo Corder from the Institute of Biomedical Science at the University of São Paulo and John Marshall from the Innovative Genomics Institute, who conducted advanced mathematical modeling to uncover crucial hidden features of the e-Drive system, including its capacity to effectively remove a group of individuals where the drive process did not occur.
