Could Crispr Flip the Switch on Insects’ Resistance to Pesticides?

While the Covid-19 pandemic raged across the world in 2020, another disease was quietly infecting more than 220 million people on the continent of Africa: malaria. That year, the disease led to more than 600,000 deaths, most of them children. Caused by the parasite Plasmodium, the illness is spread through the bites of infected female Anopheles mosquitoes.

Insecticide-treated bed nets and indoor spraying have long been some of the most effective strategies for combating the disease. But decades of using these chemicals has lessened their potency.

It happens like this: Insecticides kill off most of the mosquitoes in an area. But a small number may survive because something about their genetic makeup makes them unaffected by the pesticide. Mosquitoes within that small population mate with each other and pass on their genes to their offspring, breeding more resistant mosquitoes. In some cases, resistance has built up just a few years after the introduction of an insecticide. It makes fighting deadly mosquitoes a constant game of whack-a-mole.

Insecticides remain the frontline in fighting malaria, because interventions like building mosquito-resistant housing are still experimental, and the effort to develop a vaccine has taken decades. Last summer the World Health Organization recommended Mosquirix, the first anti-parasitic vaccine, for African children under age 5, but it is only 30 percent effective at preventing serious disease, and will take many years to achieve approval and distribution among individual nations.

Researchers at UC San Diego and the Tata Institute for Genetics and Society in India have developed a potential way to fight back: Using Crispr gene editing, they replaced an insecticide-resistant gene in fruit flies with the normal form of the gene and propagated the change through insects in the lab. The approach, known as a gene drive, is described in a January 12 paper in Nature Communications, and the team believes it can be translated into mosquitoes.

“This technology I think offers a solution to the conundrum we’re facing now, which is that there hasn’t been a new category of insecticides developed for over 30 years,” says Ethan Bier, professor of cell and developmental biology at UC San Diego and senior author of the paper. “If you can go on using the ones you’ve got by re-sensitizing the mosquitoes to those, I think that would be an enormous benefit.”

A gene drive is a type of technology that overrules the laws of heredity to spread a trait through a population more quickly than it would happen naturally, forcing that gene into a population’s offspring. In this case, the change essentially reboots the gene pool to what it was before the insects evolved resistance to a particular pesticide.

The group’s gene drive uses a molecule called a guide RNA that directs the Crispr system to remove the undesired variant of a gene—in this case, an insecticide-resistant mutation called kdr. When one parent transmits its genetic information to their offspring, a protein called Cas9 binds to the guide RNA, cuts out the mutated gene, and replaces it with the normal variant from the other parent. The normal variant is then copied and all the offspring inherit it.

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