Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans.
The genetic modification causes mosquitoes to produce compounds in their intestines that impede parasite growth, meaning they are less likely to reach the mosquito’s salivary glands and be transferred in a bite before the insects die.
So far, this technique has been shown to significantly reduce the likelihood of malaria spreading in a laboratory setting, but if it proves to be safe and effective in real-world conditions, it could offer a powerful new tool to help eradicate malaria.
The innovation, by researchers from the Transmission: Zero team at Imperial College London, has been designed so that it can be combined with existing “gene drive” technology to spread the modification and significantly reduce malaria transmission. The team is looking forward to field trials, but will fully test the safety of the new modification before integrating it with the gene drive for real-world testing.
Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation have also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by Transmission: Team Zero could be a powerful tool for reducing malaria cases even when transmission is high.
The results of the in vitro modification and modeling technique were published today in science progress.
impede the development of the parasite
Malaria remains one of the world’s deadliest diseases, with half the world’s population at risk. In 2021 alone, it infected 241 million people and killed 627,000 people, mostly children under the age of five in sub-Saharan Africa.
Study co-first author Dr Tibebo Haptiwald, from Imperial’s Department of Life Sciences, said: “Since 2015, progress in treating malaria has stalled. Mosquitoes and the parasites they carry have become resistant to available interventions such as insecticides and treatments, and funding is halted. We need to develop tools New and innovative.
The disease is transmitted between people after a female mosquito bites a person infected with the malaria parasite. The parasite then develops to its next stage in the mosquito’s intestines and travels to its salivary glands, ready to infect the next person with mosquito bites.
However, only about 10% of mosquitoes live long enough for the parasite to grow far enough to become infectious. The team aims to extend the possibilities even further, by lengthening the time it takes the parasite to develop in the gut.
Transmission: Team Zero genetically modified the main malaria-carrying species of mosquitoes in sub-Saharan Africa: Anopheles The Gambia. They were able to make it so that when a mosquito takes a blood meal, it produces two molecules called antimicrobial peptides in its gut. These peptides, which were originally isolated from honeybees and African clawed frogs, impair the development of the malaria parasite.
This caused a delay of a few days before the next stage of the parasite reached the mosquito’s salivary glands, at which time most mosquitoes in nature would be expected to die. The peptides work by interfering with the energy metabolism of the parasite, which also has some effect on mosquitoes, causing them to shorten their lifespan and reduce their ability to transmit the parasite.
Study co-first author Astrid Hormann, from Imperial’s Department of Life Sciences, said: ‘For many years, we have been trying unsuccessfully to make mosquitoes that cannot be infected with parasites or those that can eliminate all parasites with their immune system. Delaying parasite growth within mosquitoes is a conceptual shift that has allowed More opportunities to prevent transmission of malaria from mosquitoes to humans.
Publish the edit
To use genetic modification to prevent the spread of malaria in the real world, it must be spread from laboratory mosquitoes to wild mosquitoes. Natural crossbreeding may spread it to a certain degree, but since the modification has a “convenience cost” in the form of reduced lifespan, it is likely to be quickly eradicated thanks to natural selection.
Gene drive is an additional genetic trick that could be added to mosquitoes that would cause the antiparasitic gene modification to be inherited preferentially, causing it to spread more widely among any natural populations.
Because this strategy is so new, it requires very careful planning to reduce risks prior to any field trials. So Team Transmission: Zero creates two separate but compatible strains of modified mosquitoes – one with an anti-parasitic modification and the other with a gene drive.
They can then test the antiparasitic modification on their own first, and only add the gene drive once its efficacy has been demonstrated.
Dr Nikolai Windbichler, co-lead author from Imperial’s Department of Life Sciences, said: “We now aim to test whether this modification can prevent malaria transmission using not only parasites we have grown in the laboratory but also from parasites that have infected humans. That proves true, we’ll be ready to take this to field trials in the next 2-3 years.
Another weapon in the arsenal
With partners in Tanzania, the team has set up a facility to breed and handle genetically modified mosquitoes and perform some initial testing. These include the collection of parasites from locally infected schoolchildren, to ensure that the modification works against parasites prevalent in relevant communities.
They also take a full risk of evaluating any potential releases of modified mosquitoes, considering any potential risks and making sure they are accepted by the local community. But they hope their intervention will eventually help eradicate malaria.
Co-lead author Professor George Christofides, from the Department of Life Sciences at Imperial, said: “History has taught us that there is no silver bullet when it comes to fighting malaria, and therefore we will have to use all the weapons we have to get rid of it and generate more. Genetic drive is one of the weapons. The very powerful that, in combination with medicines, vaccines and mosquito control, can help stop the spread of malaria and save human lives.”
The work was funded by the Bill & Melinda Gates Foundation.