Changing the gut genes of a mosquito to spread the malaria genes to the next generation of their species shows a promise to curb malaria.
This is the finding of a feasibility study by researchers at Imperial College London, which was published today in eLife.
To finally eradicate malaria, we need to explore many new approaches, and this may be one of them. Professor George Christophides
Mosquitoes are becoming increasingly resistant to pesticides, and the parasite that causes malaria is also becoming increasingly resistant to drugs against malaria.
This has created an urgent need for new ways to fight the disease, which in 2019 is estimated to have caused 229 million cases and 409,000 deaths, most of which were young children in sub-Saharan Africa.
Gene stations are currently being tested in laboratories as a new approach. It works by creating genetically modified mosquitoes that, when released into the environment, will spread genes that reduce the mosquito populations in a particular geographic area or make the insects less likely to spread the malaria parasite.
The parasite harms
Malaria is caused by the parasite Plasmodium, which carry certain types of mosquitoes in their intestines. The team is genetically modified Anopheles gambiae mosquitoes so that, after taking a blood meal, they express small antimicrobial molecules that inhibit the development of Plasmodium parasite.
They initially inserted the gene with a fluorescent marker to locate them at three different sites in the DNA, and later removed the marker, leaving only a slight genetic change.
The team then bred the mosquitoes to see if they could reproduce successfully and stay healthy. They also tested how well the malaria parasite developed in the intestines of the mosquitoes. Their experiments provide preliminary evidence that this approach to genetic modifications can cause successful gene drives.
On the road to extinction
Senior researcher Professor George Christophides, from the Department of Life Sciences at Imperial, said: ‘To finally eradicate malaria, we need to explore many new approaches, and this could be one of them. Reducing the ability of mosquitoes to transmit the parasite responsible for the disease can have a significant impact.
“Of course, we must carefully test the safety and effectiveness of the technique before releasing genetically modified mosquitoes into the wild.”
Changing the team ‘cuts’ a functional gene in the mosquito to produce the malaria molecules. Although this change can be passed on to the offspring of the mosquito, it will currently only be passed on to some offspring.
The researchers say this means that their approach simplifies the testing of the malaria effect using these mosquitoes in the field, as the genetic change in any preliminary tests would only be transmitted to a small proportion of the mosquitoes in a local population. .
A complete ‘gene drive’ will ensure that the modification is inherited by all offspring. This will eventually require the addition of a specific component called Cas9 once the safety and efficiency have been established.
Bringing no drives one step closer
First author Astrid Hoermann, from the Department of Life Sciences at Imperial, said: “These genetic modifications are passive and can be tested in the field and undergo a rigorous regulatory process to ensure that it is safe and effective to block the parasite without to cause concern. of accidental spread in the environment. ”
Senior author Dr Nikolai Windbichler, from the Department of Life Sciences at Imperial, added: “If we think they are effective and safe, and we want them to act like a real gene drive, we just have to combine it with one that drives all on its own with the Cas9 component.
“Once we do that, it becomes self-driving, without the need for further change. Our approach therefore brings gene drives one step closer to being tested in the field as an elimination strategy for malaria. ”
The research is funded by the Bill & Melinda Gates Foundation.
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‘Conversion of endogenous malaria mosquito genes into simple non-autonomous gene replacement stations’ by Astrid Hoermann, Sofia Tapanelli, Paolo Capriotti, Giuseppe Del Corsano, Ellen KG Masters, Tibebu Habtewold, George K. Christophides and Nikolai Windbichler. in eLife.