Malaria Mosquitoes Eliminated in Lab
In lab experiments, populations of malaria mosquitoes could be eliminated by a modification that creates more make offspring.
A research team led by Imperial College London used ‘gene drive’ technology and spread a genetic modification distorting the sex ratio through a population of caged Anopheles gambiae mosquitoes.
More male offspring were produced due to the team’s modification, eventually leading to a total collapse in the population with no females being born. As such experiments are extremely effective at controlling natural mosquito populations, this represents the first successful sex-distorter gene drive ever created.
In 2018, with new interventions needed to move towards malaria eradication, there were 228 million cases of malaria and 405,000 deaths. Only 40 related species of mosquitoes can carry malaria out of the 3500 species of mosquito worldwide. The main malaria vector in sub-Saharan Africa, Anopheles gambiae mosquitoes, were used in this experiment and were subjected to the team’s modifications.
The hope is that, in the future, when within the local malaria-carrying mosquito populations, the Anopheles gambiae mosquitoes carrying a sex-distorter gene drive would be released, the population would eventually collapse as it would spread the male bias within the population.
Even before
the population collapses, the modification could have a double effect by biasing the population towards fewer females as only females bite and take blood meals and are capable of passing on malaria.Before considering to release any modified mosquitoes in the wild, more experiments are needed and this lab-based experiment was performed with only caged populations of mosquitoes.
The journal Nature Biotechnology published the results.
At Imperial, from the Department of Life Sciences, lead scientist Professor Andrea Crisanti said, “In the long-sought objective to bias the progeny of the human malaria mosquito so that only non-biting males are produced, this study represents a key milestone. With the aim of eradicating malaria, a new avenue for scientists to develop genetic vector controls of malaria is presented by having a proven driving sex-distorter.”
Creating sustained male bias
The working of the modification involves the destruction of the X chromosome during the production of sperm using a DNA-cutting enzyme, and as females require two Xs, this will lead to predominantly male offspring. There are already other sex-distorters based on similar mechanisms created before but in this, to spread through a population from a very small initial frequency in a very effective way, the new version was coupled to a gene drive.
The modification is inherited not just 50 percent as would be expected from normal mating, but nearly 100 percent of the time, as the gene spreads faster than would be expected naturally thanks to the gene drive component.
The robustness of the system is increased by coupling a sex-distorter with a gene drive. The modification can spread effectively as there is no detriment to the males, which means the mosquitoes are more likely to mate and pass on their genes.
This was seen to have huge potential to control malaria-carrying mosquitoes in the field as with only a small fraction of the initial mosquitoes possessing the gene (2.5% release frequency), the male-biased gene was shown to spread quickly through the population without being stopped by resistance.
Moving to the next phase
The team has a line of mosquitoes that have gone onto larger cage trials that more closely match natural conditions as they had previously created modified Anopheles gambiae mosquitoes that spread female infertility.
The new male-biased mosquitoes have the added benefit of reducing the proportion of biting females at an earlier stage and leads to population crashes faster than the female-infertility mosquitoes. The fate of the gene drive may change due to the mating dynamics, competition for food, and other ecological factors as they will now go into larger cage trials.
Dr. Alekos Simoni, Co-lead author on the new paper said: “It is great to see this line of mosquitoes move onto the next phase of the project and the new result is very exciting. Nobody knew if it would work when we started. I am proud that we used a novel theoretical idea to have the potential to save millions of lives by transforming it into something that was shown to work in the lab.”
Dr. Drew Hammond, Co-lead author added: “This result allows us to hit malaria before it can be transmitted and we have been working towards for over a decade. It could be a game-changer in the fight to eliminate malaria if gene drive technologies work in the wild, as of now, we are still testing these strains in the lab.”
Under the Target Malaria project, this work was funded by the Bill & Melinda Gates Foundation.
