Genetic technology to prevent crossbreeding could safely harness the power of gene forcings

The advent of the genetic age offers the tantalizing prospect of being able to genetically modify animals, such as parasites and disease vectors, to reduce the damage they cause to society. However, any technology capable of making a difference on a significant scale could also cause serious damage if it got out of hand.

Gene drive is one such technology. These genetic changes are designed to spread rapidly in a population and rely on the CRISPR-Cas9 gene editing system to create a duplicate copy of the gene drive on the partner chromosome. This means that all descendants inherit the gene, compared to only 50% by normal genetic inheritance.

However, the effect of releasing such genetic forcings in nature is cause for concern. Unintended consequences, potentially due to mutations or ecological changes, could be irreversible.

This has led geneticists to seek new versions of gene drives that can prevent unrestricted spread by preventing the modified animals from interbreeding with the wild population. The approaches developed previously have serious limitations, such as not functioning in multicellular organisms, leading to high fitness costs, or functioning incompletely.

A way to control populations

Now, geneticists have developed a new approach called synthetic postzygotic barriers exploiting CRISPR-based incompatibilities for engineered species (SPECIES) that prevent crossbreeding. SPECIES uses an adapted form of the Cas9 protein which is used to target gene sequences in the CRISPR editing technique. The adapted Cas9 recruits the cell’s transcriptional machinery to genes essential for development, causing the cell to overexpress the gene to a lethal degree.

Scientists at the University of California at San Diego modified the genome of fruit flies using CRISPR-based technologies to create eight reproductively isolated species. Image courtesy of Akbari Laboratory, UC San Diego.

Researchers can prevent this deadly overexpression in modified SPECIES organisms by mutating the promoter regions of genes to stop Cas9 binding. If a modified animal attempted to breed with a wild type, the offspring would not survive because Cas9 would target the developing wild type gene, triggering overexpression.

“Genetic transmissions can potentially spread beyond intended borders and be difficult to control. SPECIES offers a way to control populations in a very safe and reversible manner,” said Omar Akbari, PhD, associate professor at the University of California, San Diego Division of Biological Sciences and lead author of the article, in a statement.

In the new study, the team described how they generated eight modified SPECIES of fruit flies that could not mate with each other or with the wild-type fly, Drosophila melanogaster. By targeting two to three genes per SPECIES, the researchers hope this will ensure that natural mutations do not allow crossbreeding.

The approach reflects the natural formation of new species, where distinct populations of the same species progressively evolve in divergent ways until their genetics are no longer compatible for reproduction.

“Even though speciation occurs systematically in nature, creating a new artificial species is actually quite a significant bioengineering challenge,” said Anna Buchman, PhD, Akbari lab researcher and lead author of the article. “The beauty of the SPECIES approach is that it simplifies the process, giving us a defined set of tools that we need in any organism to elegantly induce speciation.”

Harness the power

One of the most sought-after targets for gene drive technology is to prevent the spread of malaria by mosquitoes. Genetically modified mosquitoes that cannot carry the disease could be used to overwhelm the wild population and stop its spread.

Since the gene drive of SPECIES cannot proliferate through breeding with wild-type animals, a modified SPECIES must be released multiple times to dominate the population. If the new SPECIES exceeds a certain threshold percentage of the overall population, it can replace the wild type.

However, below this threshold, the wild type can regain the upper hand if the releases stop. This is because wild-type animals would have a reproductive advantage over modified SPECIES due to the low fitness costs caused by the system.

“Since SPECIES are incompatible with wild-type mosquitoes, their populations can be controlled and reversed by limiting their population threshold below 50%. This gives you the ability to limit and reverse its spread if you do so. wish, ”Akbari said. “Essentially, this allows us to harness the full power of gene drives – such as disease elimination or crop protection – without the high risk of uncontrollable spread.”

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