Resistance to Gene Editing in Insects Hampers Use of Crispr-Cas9 to Tackle Malaria

Resistance to Gene Editing in Insects Hampers Use of Crispr-Cas9 to Tackle Malaria

CRISPR-Cas9 has been shown to have great potential for treating genetic disorders and other diseases in humans and livestock. There is also hope that the gene editing tool could be used to tackle insect-borne diseases such as agricultural blight and malaria.

However, researchers from Indiana University have discovered that disease carrying insects have genetic and behavioral qualities that may prevent gene editing from serving as a potential population control method.

CRISPR-Cas9 is a gene editing tool that allows researchers to accurately edit genomes without major off-target effects. While the technology can be used to spread infertility in insect populations, the recent study has uncovered issues that would hamper the effectiveness of the technique in wild populations of insects.

The research team used genetic and statistical analyses to show that insect species are resistant to genetic manipulation. Michael J. Wade, Distinguished Professor of Biology at IU Bloomington, said while the technology can be used to spread infertility in insect populations, his research team has identified a number of stumbling blocks. “We found that small genetic variation within species, as well as many insects’ tendency to inbreed, can seriously impact the effectiveness of attempts to reduce their numbers using CRISPR technology.”

While there are only small numbers of insects that have genetic variants resistant to editing, the team’s study on flour beetles – Tribolium castaneum – showed that insect populations would rapidly revert to wild populations following attempts to control populations.

If a gene edit was performed, such as the introduction of a new genetic variant that resulted in female mosquitos laying fewer eggs, it would likely be eradicated from a population within a few months. Even if a gene drive is highly effective and can be used to spread genes at a rate of 90%, it would still not be sufficient.

The study on four varieties of flour beetles revealed genetic variance rate as high as 28%, but a statistical analysis showed that even a variance rate of 1% would be high enough to ensure that any introduced variant would be eliminated from a population within 6 generations, given the typical rate of inbreeding in wild populations of mosquitos.

In order for any CRISPR-Cas9 gene edits to be used as an effective method of population control, the targeted species would need to be extensively studied to determine the genetic variation in a population. Wade said, “This will help predict the effectiveness of the method, as well as provide insight into ways to circumvent natural genetic variation through the use of Cas9 variants with an altered sequence specificity.”

The research study – CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations – has recently been published in the Journal Science Advances.

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