Male-Biased Gene Eliminated Malaria Mosquitoes Quicker in the Lab: Study
Fri, December 9, 2022

Male-Biased Gene Eliminated Malaria Mosquitoes Quicker in the Lab: Study


A group of researchers found a way to reduce the number of malaria vectors. Through genetic modification, they were able to raise the male population of malaria-spreading mosquitoes.

The genetic modification to decrease female and increase male Anopheles gambiae mosquitoes was led by Imperial College London (ICL), a public research university in London. Researchers modified the genetics of the vectors and successfully distributed that altered gene in lab mosquitoes. The result was more male mosquitoes that triggered the population collapse of the vectors. They published their findings in the journal Nature Biotechnology.

Boosting Male Mosquitoes to Crash Vector Population

According to the World Health Organization (WHO), a specialized agency of the United Nations, malaria is a parasitic disease caused by the Plasmodium parasites. The parasites can be spread by Anopheles mosquitoes, specifically, the female population. As such, female Anopheles mosquitoes are the vectors of malaria in endemic regions. The vectors can spread five parasite species of malaria, but P. falciparum and P. vivax are the greatest threats to human health.

At ICL, researchers applied genetic manipulation to induce population collapse on Anopheles mosquitoes. Instead of directly killing every single mosquito, they edited the genes of the vectors to increase the probability of male offspring and shrink the odds of female offspring, simultaneously. Eventually, the limited numbers of females resulted in the elimination of future generations, effectively destroying the vector population, at least, in the lab settings.

"This study represents a key milestone in the long-sought objective to bias the progeny of the human malaria mosquito so that only non-biting males are produced. Having a proven driving sex-distorter opens a new avenue for scientists to develop genetic vector controls of malaria with the aim of eradicating the disease," a lead author of the study and scientist from the Department of Life Sciences at ICL.

In the study, the team utilized an enzyme capable of cutting DNA. This enzyme could destroy the X chromosome that would normally be present during sperm production. The destruction of the chromosome altered the chances of the gender in Anopheles mosquitoes, favoring males. While the genetic modification method was not unique, researchers integrated it with a gene drive to distribute the alteration throughout the vector population.

Due to the gene drive, gender distortion increased significantly. Researchers estimated that the chance of inheriting the modified gene is almost 100% of the time, compared to the 50% in the normal mating scenario. Moreover, the integration substantially improved the performance and distribution of the gene in the population, meaning the altered gene would be sustained in male mosquitoes since their ability to mate was never changed. This ensured that the gene would be passed down to the next generation until the extinction of females.

In the 2.5% release frequency within lab settings, researchers determined that the gender-biased gene was distributed quickly in the population. The gene was not hindered by any resistance at the time of the experiment, which expressed the method's potential in controlling malaria in real-world settings. Compared to the team's previous method, the distribution of female infertility, the male-biased gene collapsed the population at a faster rate.

Researchers are setting up the next series of experiments using the male-biased gene. Some of the conditions in those experiments include large cage trials to mimic natural dynamics in the wild, such as food competition, ecological factors, and even mating elements.



The Global Fight against Malaria

According to the World Malaria Report 2019 by the WHO, about 228 million cases of malaria were reported worldwide in 2018. It was lower than the 251 estimated cases reported in 2010 and 231 million cases in 2017. The comparison showed that global efforts against the disease were improving conditions in endemic areas.

Based on that report, the WHO confirmed that 93% or 213 million malaria cases were in the African Region. It was followed by the Southeast Asia Region at 3.4% of all cases and the Eastern Mediterranean Region at 2.1% of all cases. Within the African Region, 19 nations in Sub-Saharan African and India accounted for nearly 85% of the global burden due to malaria, while six nations accounted for 54% of all malaria cases in the world. As of 2018, the six nations were Nigeria at 25% of all cases, the Democratic Republic of the Congo (DRC) at 12%, Uganda at 5%, Côte d'Ivoire at 5%, Mozambique at 5%, and Niger at 5%.

When it comes to the incidence rate, the decline of malaria cases on a global scale was from 71 cases per 1,000 population at risk in 2010 to 57 in 2018. But the downward trend stalled in recent years. From 2014 to 2018, the incidence rate remained at 57 cases per 1,000 people at risk of malaria. This showed that the current global response could no longer do more without additional or innovative methods. The stalled decline rate might also suggest new challenges happening in endemic areas.



For the parasite species, the report indicated that P. falciparum remained the most common malaria parasite in the African Region, accounting for 99.7% of all cases in 2018. In the Southeast Asia Region, the species accounted for 50% of all cases, 71% in the Eastern Mediterranean Region, and 65% in the Western Pacific Region. But P. vivax still had a major cut of cases, accounting for 47% in India and 75% in the Region of the Americas.

A total of 11 countries in 2018 were assessed with the highest burden due to malaria. These countries were estimated to account for 155 million cases in 2018, lower than the 177 million in 2010. Out of 11 countries, about 40% of the population at risk of malaria were sleeping under long-lasting insecticidal nets. Uganda had the highest population percentage protected by these nets at 80% while Nigeria had the lowest population percentage at 40%. Despite the stalled decline rate of malaria cases, there were countries awarded with elimination in 2018. Both Paraguay and Uzbekistan were awarded with the WHO certification of elimination, while Algeria and Argentina achieved the certification in early 2019.

The gene involved in the study shows promise in controlling the spread of malaria. However, many aspects must be examined before it can be deployed in the wild. Since the technique uses gene alteration, there is no precise way to predict its influence in real environments, wherein hundreds of thousands of animals, plants, and other lifeforms are engaged 24 hours a day. So, knowing if the gene is exclusive to Anopheles mosquitoes may limit potential consequences in wildlife.