Researchers at Imperial College London have made a breakthrough in the application of genetically engineering mosquitoes to control the spread of malaria.
The method involves a replicating gene edit in female mosquitoes that in lab experiments are inherited by all descendants without the development of resistance.
It took one year in the large caged population for the ‘gene drive’ to spread to the entire population.
Co-lead author, Dr Drew Hammond of Imperial’s Life Sciences Department and the John Hopkins Malaria Research Institute described the gene drive as a game-changer in eliminating the disease.
Hammond said: “Sadly, researchers estimate that COVID-19 related disruptions may have doubled mortality from malaria in 2020, threatening a setback of several decades.”
What is a CRISPR gene drive?
CRISPR editing uses an enzyme extracted from bacteria to detect and destroy a targeted sequence of DNA.
A variant of the enzyme, called Cas9, allows for this process to be coupled with the replacement of the destroyed segment with a new sequence of DNA, allowing for the editing of a genome within a living organism.
In the case of malarial mosquitoes, this modification can alter the shape of certain proteins to prevent malaria from binding to mosquitoes or alter the fertility of mosquitoes to control their population.
Since malaria can only be spread by a female mosquito and not between humans, reducing the mosquito population or preventing them from carrying malaria would swiftly allow for the extermination of the disease.
A long-time obstacle to this approach has been that any genetically modified mosquitoes released into the wild would have the modified genes diluted when breeding with the wild population.
The gene drive solves this by attaching the genetic instructions for a CRISPR complex that will overwrite the wild gene with the modified one, forcing it to be inherited.
Previous experiments of this gene drive technology saw the development of resistance in the population.
This occurs due to mutations that change the area targeted by the gene drive, making it no longer recognised.
The solution found by the research team was to target a vital section of the genome that is highly resistant to change.
Hammond added: “We identified a region of DNA that is almost exactly the same in almost every single African malaria mosquito ever tested in nature, but is not the same in mosquitoes not capable of transmitting malaria.”
The doublesex gene, when interfered with causes what would be female mosquitoes to develop intersex bodies, becoming infertile.
Dr Hammond explained that spreading this infertility through the population of malaria carrying mosquitoes would allow them to be displaced by the mosquito species that are incapable of carrying malaria, with virtually no risk that other species will develop the ability to carry the disease.
The protoplasm that causes malaria, he said, had to evolve simultaneously to survive in both humans and the mosquito, and that it would be difficult for it to adapt this.
He added: “These two interactions can take hundreds to thousands of years to evolve. A gene drive can work so quickly that we don’t believe a shift in the vector species would pose anywhere near the threat posed by the current malaria mosquitoes.
“What is important is that other methods of vector control must continue to be used and developed alongside gene drives so that malaria can be completely eradicated.”
