Using CRISPR to Disrupt Malaria-Spreading Mosquitoes

Category Science

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In a paper published in Science Advances, researchers from the University of California in San Diego proposed a novel method dubbed Ifegenia to disrupt malaria-spreading mosquitoes. Ifegenia works by using gene editing tools, specifically by genetically encoding a Cas9 nuclease with a guide RNA to target the femaleless gene, causing death of all female larvae. The males, however, will carry and spread the genetic mutations. Ifegenia is not likely to be hindered by genetic resistance, but it could have unintended consequences.

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Though at least one vaccine for malaria is in use, it remains one of the deadliest diseases in the world. Almost half of the world’s population lives in areas where malaria transmission occurs, and an estimated 619,000 people died of the disease in 2021. Worse yet, the vast majority of cases leading to death are in young children.

Researchers from the University of California in San Diego may have found a way to reduce this burden of disease. They used the gene editing tool CRISPR to alter a gene that controls sexual development in mosquitoes. Male mosquitoes don’t bite humans; it’s the females that spread malaria and other diseases. The UCSD team’s method uses gene editing to kill all female mosquito offspring within a given population of the insects.

As of July 14th 2023, the estimated global death rate of malaria is 619,000 individuals.

The mosquito species in question is Anopheles gambiae, commonly called the African malaria mosquito and described as "the most efficient vector of human malaria." They’re anthropophilic, meaning they like human blood more than animal blood, and they thrive in hot climates with a lot of moisture. Why such an insect exists in the first place is hard to comprehend, is it not? .

But there’s hope. In a paper published last week in Science Advances, the researchers described a method dubbed Ifegenia. The word is an acronym for "inherited female elimination by genetically encoded nucleases to interrupt alleles." The team noted they chose the name in honor of a character from Greek mythology: Iphigenia was sacrificed by her father, King Agamemnon, in order to win a battle.

The most efficient vector for human malaria is the Anopheles Gambiae mosquito.

The Ifegenia system targets a gene called femaleless, or fle. It works by genetically encoding a Cas9 nuclease (the "molecular scissors" CRISPR uses to cut a strand of DNA) in one mosquito family and a guide RNA in another family. When mosquitoes from the two different families mate, their offspring end up with mutations to the fle gene that cause all female larvae to die.

The males, meanwhile, not only live, they carry and spread Ifegenia; that means any female they impregnate will only have male offspring—which will also carry and spread the genetic edit to keep preventing disease-spreading females from being born.

CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats.

Within a given population, it’s only a matter of time until there’s no females left—and thus no way to spread malaria. Since its Cas9 and guide RNA components are separate until mating occurs, Ifegenia isn’t likely to be hindered by genetic resistance and other issues common in gene drive technology.

"Ifegenia can achieve robust temporary population suppression over a wide range of release parameter values, permitting rebound of native populations after ceasing releases," the researchers wrote. It seems like once you get rid of the pests there’d be no reason to bring them back, but the authors note it may make sense to do so in areas where their system eliminates malaria but there are "ecological concerns" about completely stamping out the insect.

Instead of altering mosquitoes directly, the Ifegenia system alters the genes in their offspring.

As a lifelong mosquito magnet, I’m all for eradicating the evil-doers from the face of the Earth. But also, getting rid of a species—even a universally detested one—could have impacts we’re not aware of, both in the present and further down the line. We should always be wary of how seemingly helpful projects can have unintended consequences.

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