Gene editing mosquitoes so they die before malaria parasites can develop inside them could stop the spread of the deadly parasite entirely, according to lab studies and computer models
Anopheles gambiae mosquitoes can carry malaria
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Malaria-carrying mosquitoes have been genetically modified in a way that slows the development of any malaria parasites inside them and also reduces the lifespan of the mosquitoes. The result is that the modified insects die before they can spread the disease.
Lab studies and computer models suggest this could completely stop the spread of the deadly parasite, says team member George Christophides at Imperial College London.
“The combination of the two will eliminate malaria transmission,” he says.
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For the approach to work, something called a gene drive would have to be used to spread the required genetic modification throughout wild mosquito populations. This is a mechanism that leads to a specific piece of DNA being inherited by all offspring, rather than just half as usually happens. The gene drive makes that piece of DNA spread in a population even if it is disadvantageous.
No engineered gene drive has yet been used in the wild – although naturally occurring versions exist – but CRISPR-based gene drives have been successfully tested in caged mosquitoes.
Read more: Can we finally wipe out malaria with a vaccine 37 years in the making?
Researchers in Tanzania are now altering local mosquitoes in the same way as the researchers in London to see how well the modification works against local malaria parasites. If these studies are a success, the teams hope to collaborate on field trials in Tanzania, but for now the work is confined to labs.
“We are not releasing anything,” says Christophides.
The new work relies on the fact that it takes between 10 and 12 days for malaria parasites to develop within a mosquito and reach its salivary glands. Only at that point can mosquito bites infect people, yet in the wild Anopheles gambiae mosquitoes, which can carry malaria, typically live for just 10 days.
“So you can crash the entire transmission cycle by delaying parasite development,” says Christophides.
To do this, his team genetically modified A. gambiae mosquitoes so that cells in their guts secrete two small proteins previously shown to delay parasite development. One of these proteins comes from the African clawed frog, the other from honeybees.
When the modified mosquitoes are infected, it takes a few days longer before malarial parasites can be detected in the heads of the mosquitoes, the team has shown. What’s more, the change also shortens the lives of mosquitoes by a couple of days, says Christophides, further reducing the chances of any mosquitoes surviving long enough to become infectious.
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There are two potential problems with the approach. As a gene drive spreads the modification, there would be a risk of malarial parasites evolving resistance to the two proteins. To avoid this, it will be important to spread the modification among mosquitoes as much as possible, says Christophides. The faster a parasite population collapses, the lower the odds of resistance evolving.
It is also possible that mosquitoes evolve in a way that stops the gene drive working. The gene drive would be designed to minimise this risk, says Christophides.
Other groups are working on gene drives designed to wipe out mosquito populations, for instance by making all female offspring infertile while males remain fertile and continue spreading the gene drive.
These two approaches could potentially be used together. For instance, a killer drive could be used to wipe out mosquitoes in a region and then any that survive or come in from another area could be modified by another drive to prevent them spreading malaria.
“We believe that both of them can contribute,” says Christophides.
In Brazil, millions of genetically modified male mosquitoes are already being released to reduce wild mosquito numbers. These GM mosquitoes carry a gene that kills the offspring of any female mosquitoes they mate with. There is no evidence that this gene persists in the wild.
Malaria still kills nearly half a million people every year, mainly children. Last year, a malaria vaccine was approved for the first time and another one could be approved soon, but these are only partially effective.
Journal reference: Science Advances, DOI: 10.1126/sciadv.abo1733
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