Since insecticides are the most prevalent way of controlling crop damage from pests, their overuse has rendered pests insecticide-resistant. When beetles, moths, or other insects develop genetic mutations against insecticides, vector controllers are compelled to use poisonous compounds.
The increased use of such compounds kills ecologically important insects and pests, which poses a significant risk to human health and damage to the environment.
In efforts to counter these challenges, geneticists at the University of California San Diego have developed CRISPR-based gene-drive technology, e-Drive. The e-Drive genetically modifies the insecticide-resistant genes and replaces them with pesticide-susceptible genes.
This novel system replaces mutated genes by using the biased inheritance of specific genetic variants known as alleles. Researchers have designed it so that it disappears later, leaving behind the original “wild type” version of the gene.
The lead author, Ethan Bier, says, “We have developed an efficient biological approach to reverse insecticide resistance without creating any other perturbation to the environment. The e-Drive is programmed to act transiently and then disappear from the population.“
According to the study published in Nature Communications, researchers created a genetic “cassette,” a novel group of DNA elements, and inserted it into fruit flies. This was just a demonstration that this technology could be applied to other insects.
This e-Drive cassette targets a gene known as the voltage gated sodium ion channel or vgsc, which is vital for proper nervous system functioning. The cassette binds to Cas9 DNA protein and penetrates vgsc insecticide resistance gene. This gene is then replaced with its native natural form.
Researchers assert that when a cassette gene is inserted into a target insect, its mating passes the pesticide-susceptible gene to its offspring. Since the gene-drive systems can continuously spread unchecked, geneticists can impose restrictions through limited viability or fertility.
For instance, the cassette inserted on the X-chromosome reduces the mating success of males. This results in reduced offspring. The frequency of the cassette in the population eventually declines and eventually vanishes from the population.
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During the lab results, researchers successfully converted native genes in 8 to 10 generations.
“Because insects carrying the gene cassette are penalized with a severe fitness cost, the element is rapidly eliminated from the population, lasting only as long as it takes to convert 100 percent of the insecticide-resistant forms of the target gene back to wild-type,” says Ankush Auradkar.
Researchers have asserted that the self-eliminating nature of the e-Drive makes it fit to re-introduce as and when needed. Additionally, the team asserted that it could be used to limit the growth of disease-spreading mosquitoes.
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Journal Reference
- Auradkar, A., Corder, R. M., Marshall, J. M., & Bier, E. (2024). A self-eliminating allelic-drive reverses insecticide resistance in Drosophila leaving no transgene in the population. Nature Communications, 15(1), 1-10. DOI: 10.1038/s41467-024-54210-4
