Mutated mosquitoes do not transmit malaria

Malaria remains a substantial global health challenge, causing approximately half a million deaths each year. Mosquitoes kill more people each year than any other animal. In 2023, mosquitoes infected a reported 263 million people with malaria, leading to nearly 600,000 deaths, 80% of which were children. Mosquitoes are smart and have adapted resistance to insecticides and the parasites within mosquitoes that cause malaria have become resistant to drugs.

Scientists have genetically edited mosquitoes so they can’t transmit malaria. and made the mutation self-replicating[1].

Now, researchers have developed a new method that genetically blocks mosquitoes from transmitting malaria. They created a CRISPR-based gene-editing system that changes a single molecule within mosquitoes, a minuscule but effective change that stops the malaria-parasite transmission process.

Genetically altered mosquitoes are still able to bite those with malaria and acquire parasites from their blood, but the parasites can no longer be spread to other people. The new system is designed to genetically spread the malaria resistance trait until entire populations of the insects no longer transfer the disease-causing parasites.

An explanation
The mosquito fibrinogen-related protein 1 (FREP1) helps mosquitoes to develop and feed on blood when they bite. The naturally occurring FREP1Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito.

Scientist now have generated congenic strains of Anopheles stephensi, edited to carry either the parasite-susceptible FREP1L224 or the putative-refractory FREP1Q224 alleles. The FREP1Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs.

The protective FREP1Q224 allele can be efficiently driven into FREP1L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.

A reaction
Replacing a single amino acid in mosquitoes with another naturally occurring variant that prevents them from being infected with malarial parasites — and spreading that beneficial trait throughout a mosquito population — is a game-changer. It’s hard to believe that this one tiny change has such a dramatic effect.

The beauty of this approach lies in leveraging a naturally occurring mosquito gene allele. With a single, precise tweak, they have turned it into a powerful shield that blocks multiple malaria parasite species and (likely) across diverse mosquito species and populations.

In a series of follow-on tests, the scientists found that, although the genetic switch disrupted the parasite’s infection capabilities, the mosquitoes’ normal growth and reproduction remained unchanged.

While the researchers demonstrated the effectiveness of the L224-to-Q224 switch, they don’t yet fully grasp why this change works so efficiently. Ongoing research into how the Q224 amino acid blocks the parasite’s infection transit route is underway.

[1] Li et al: Driving a protective allele of the mosquito FREP1 gene to combat malaria in Nature - 2025. See here.