Scientists think they may have found a way to delete a gene in mosquitos that makes them the perfect malaria host.
Published in PLOS Pathogens, it’s the first time researchers have been able to show that deleting a specific gene in mosquitos can make the bugs highly resistant to malaria parasites, reducing the likelihood of transmission to humans.
"Our study shows that we can use this new CRISPR/Cas9 gene-editing technology to render mosquitoes malaria-resistant by removing a so-called host factor gene," says senior author George Dimopoulos in a statement. "This gives us a good technological platform for developing advanced malaria-control strategies, based on genetically modified (GM) mosquitoes unable to transmit the disease, and for studying the biology of malaria parasites in their mosquito hosts."
CRISPR works by targeting certain genes responsible for certain traits. When found, one of the enzymes produced by CRISPR called Cas9 binds to the DNA, cuts it, and shuts off that targeted gene. This is exactly what researchers at Johns Hopkins Bloomberg School of Public Health’s Malaria Research Institute did to a gene called fibrinogen-related protein 1 (FREP1), which encodes immune proteins that help the malaria parasites survive in a mosquito’s gut before going on to the developmental stage required for transmission to people. In these modified mosquitos, the plasmodium parasite responsible for malaria was less likely to survive and multiply.
Only female mosquitos, called anophelines, carry the FREP1 gene. If a mosquito bites a person already infected with malaria, it can then become infected and spread the parasite to other people – even in places where malaria has been completely eradicated.
There were more than 200 million malaria cases worldwide in 2016, with 445,000 deaths, according to the World Health Organization. While there is a vaccine available, researchers say it is only temporary, offers partial protection, and the supply is limited. GM mosquitos could provide an alternative.
"The resistance to malaria parasites that's achieved by deleting FREP1 is remarkably potent," Dimopoulos said. "If you could successfully replace ordinary, wild-type mosquitoes with these modified mosquitoes, it's likely that there would be a significant impact on malaria transmission.”
Replacing ordinary mosquitos with the modified ones hasn’t yet been attempted, but that could be on the horizon via a “gene drive”. This is when DNA modifications are spread quickly into wild populations through interbreeding, essentially “hacking” the conception process and pushing the modified gene into nearly all of the offspring.
But deleting FREP1 from mosquitos does come with consequences: Modified mosquitos were slower to develop into adulthood, less likely to take blood meals when given the opportunity, and laid less viable eggs – all things that could have ramifications on natural ecosystems that rely on the nagging insect.