Swatting at mosquitoes is a great start, but if we really want to cut down on the hundreds of millions of malaria cases they cause every year, we're going to need some more effective weapons. Now, researchers from Johns Hopkins have used the CRISPR/Cas9 gene editing tool to engineer mosquitoes that are highly resistant to the malaria parasite, by deleting one specific gene.
      According to the latest report from the World Health Organization, there were 216 million cases of malaria in 2016, resulting in 445,000 deaths. Female Anopheles gambiae mosquitoes are the primary culprit, and over the last few years scientists have engaged in all kinds of genetic warfare against the parasites and the insects that spread them.
      In 2011, a UC Irvine team modified mosquitoes so that females of the species couldn't fly. They would die where they hatched, while the males would fly off, mature and mate with wild females which would unknowingly pass the deadly mutation down to their offspring. Other genetic tweaking turned the insects' immune systems against the malaria parasite, made mosquitoes unable to sniff out humans, or crippled larvaeby silencing crucial development genes.
      The new study, conducted by researchers at Johns Hopkins Bloomberg School of Public Health, targeted a gene called FREP1. This gene encodes for a specific immune protein that, for reasons not fully understood, helps the malaria parasite survive in the mosquito's gut. By snipping out FREP1 using the genetic scissors of CRISPR/Cas9, the team was able to reduce the likelihood of the malaria parasite surviving long enough to mature to the stage where it can harm humans.
      "Our study shows that we can use this new CRISPR/Cas9 gene-editing technology to render mosquitoes malaria-resistant by removing a so-called host factor gene," says George Dimopoulos, senior author of the study. "The resistance to malaria parasites that's achieved by deleting FREP1 is remarkably potent."
      The technique was able to reduce the number of mosquitoes infected with malaria, and the researchers also found no trace in the bugs' saliva glands of sporozoites – the stage of the parasite that is transferred to humans through the bite.
      The genetic edit wasn't perfectly neat though. The team found that the engineered mosquitoes developed more slowly than their natural counterparts, were less likely to feed on blood and laid fewer eggs that were less viable. If the modified mozzies were released into the wild in this state, natural selection could wipe them out before they got the job done.
      "We're now making mosquitoes in which FREP1 will be inactivated only in the adult gut," says Dimopoulos. "We predict that when we do that, the mosquito won't suffer the same fitness costs."
      Once those kinks are ironed out, the genetically-modified mosquitoes could be released into the wild to spread their malaria resistance through the natural population. The researchers think that this could be a viable strategy, since the gene edits they've performed don't impact the insects' ability to survive and breed.
      "If you could successfully replace ordinary, wild-type mosquitoes with these modified mosquitoes, it's likely that there would be a significant impact on malaria transmission," says Dimopoulos.
The research was published in the journal PLoS Pathogens.