CRISPR editing on mosquitoes could save hundreds of lives from malaria – but there’s a catch
In the whole of nature, you’ll find few less popular creatures than the mosquito. In an absolute best-case scenario, they’re an annoying pest. At worst, they’re a menace to humanity, responsible for the death of almost 500,000 humans every year through the inadvertent spread of Plasmodium – the parasite that causes malaria.
The Bill & Melinda Gates Foundation has previously considered wiping out the pests for the good of humanity, and one of the possible answers was via CRISPR gene editing. However, such a move would divide conservationists – so what if CRISPR could be used not to kill mosquitoes, but to prevent them from spreading malaria to humans?
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Such an approach has now seen some success in the labs of Johns Hopkins University. Published today in PLOS Pathogens, the researchers found that with a tweak to the Anopheles gambiae mosquito’s fibrinogen-related protein 1 (FREP1) gene, Plasmodium can be prevented from reaching the bug’s salivary glands, in turn stopping it from reaching human bloodstreams.
The CRISPR edit significantly suppressed infection levels in mosquitoes with both human and rodent Plasmodium parasites – meaning that theoretically, the threat of spreading malaria can be considerably reduced without wiping out the species entirely.
“Wiping mosquitoes out could be logistically and technically a very complex and challenging task, but not necessarily unethical since the removal of one or a few mosquito species would not have any ecological impact,” lead author George Demopoulos tells me via email. “The replacement of a malaria-transmitting mosquito population with one that does not transmit the parasite may be a more permanent solution, not requiring continuous releases of GM mosquitoes or continuous spraying with insecticides.”
“May be” is an important caveat here, because there is a drawback to the CRISPR modification. Researchers found that mosquitoes with the deactivated FREP1 gene were less effective at being mosquitoes – they were worse at collecting blood, had weaker fertility rates and a lower egg-hatching rate. In other words, in a world of survival of the fittest, these mosquitoes were unlikely to go forth and multiply.
Why would deactivating one gene have this impact? “Most likely because FREP1 play a role in mosquito gut function that related to blood feeding,” Demopoulos tells me. “The lower fertility and some of the other side effects can be linked to that. FREP1 may also play other roles in mosquito biology.”
The researchers’ solution is to try to find a way to only inactivate FREP1 in the guts of females, in a bid to reduce the fitness hit, while maintaining the resistance to Plasmodium.
Why female mosquitoes? “Since only the female mosquito transmit the parasite, and FREP1 appears to be important for parasite infection in the gut tissue,” Demopoulos explains. “We will attempt to inactivate the gene in the female gut only, hoping that this strategy would minimise the observed fitness costs.”
So if this proves successful, how many generations would it take to wipe out the malaria-carrying mosquitoes? That’s “impossible to calculate” according to Demopoulos, as it would depend on “the density and prevalence of mosquitoes in nature, and the efficacy of the replacement strategy”. Despite this, Demopoulos believes this is a process that can be measured in days and months, rather than years and decades. “One would aim for a strategy that would only require a few months to half a year,” he says.