The best way to get rid of an infectious, mosquito-spread disease like malaria may be to beat it at its own game.

Using an infectious DNA construct—that spreads through mosquito chromosomes and progeny alike—researchers have created a population of biting insects that appears almost completely resistant to the malaria-causing parasite, Plasmodium falciparum. The findings, published Monday in the Proceedings of the National Academy of Sciences, could signal that researchers are close to using the powerful and controversial genetic tool in wild populations where it could help wipe out malaria once and for all.

“We don’t think that this technology alone is going to be responsible for eradicating malaria,” Anthony James, a vector biologist at the University of California, Irvine, told Ars. “This is going to be a combined effort.” But, he said, his group is hopeful that people who live in malaria-riddled countries will want to give these engineered mosquitoes a try.

Of course, James and his colleagues are far from the first to try using genetically engineered mosquitoes to defeat malaria—and other mosquito-spread diseases, such as dengue. But the infectious genetic trick sets these mosquitoes apart. Whereas other modified mosquito strategies would require periodically releasing large numbers of engineered insects to make sure the genetics take hold in a wild population, these new mosquitoes can theoretically take over a wild population completely, forever—which is good, but also worrying to some.

That controversial infectious DNA construct is a type of CRISPR/Cas9 gene drive system, which contains several genes that allow it to insert itself into a chromosome and make mosquitoes resistant to malaria parasites.

The CRISPR/Cas9 system, winner of the 2015 Breakthrough Prize, directs the cutting and pasting of the construct into a chromosome. Basically, the system works by having an RNA molecule that’s engineered to recognize a specific spot in the mosquito genome. Then, the Cas9 enzyme snips that spot. Natural DNA-repair mechanisms will try to patch up the broken DNA using a template that contains a similar DNA sequence. Because the rest of the mosquito gene drive system is engineered to contain similar sequences to those naturally found near the snip-spot, the mosquito’s repair system is tricked into using the construct as the patch. Thus, the whole gene drive system gets copied and inserted into the chromosome.

In addition to the CRISPR/Cas9 system, the construct also carries two genes that make the mosquitoes resistant to P. falciparum, one of the parasite species that causes malaria in humans.

Of course mosquitoes, like humans, have two sets of chromosomes—one from each parent. And lodging the DNA construct into just one chromosome would normally mean that only 50 percent of mosquito offspring will get a copy. But because the whole gene drive construct gets inserted into the chromosome, the CRISPR/Cas9 system can repeat the process again. The result is a second full copy of the construct at the same spot on the paired chromosome—and assurance that all of that mosquito’s young will get one, too.

In the new study, James and colleagues got the gene drive system working in Anopheles stephensi mosquitoes, which spread malaria in India and Africa. In lab experiments, the engineered mosquitoes that mated with normal insects passed on their malaria-resistance genes to about 99 percent of their progeny.

Though the researchers stopped short of directly showing that the mosquitoes could resist malaria parasites, they demonstrated that the anti-parasite genes were active. Those genes were proven effective at making mosquitoes resistant to malaria in previous studies.

James said he and his colleagues next want to tweak and perfect the system, which he said should easily transfer to other mosquitoes. It could be as little as a year before the next batch of mosquitoes is ready. But, he cautioned, many hurdles, including government regulation and community acceptance of the genetically engineered mosquitoes, remain.

Indeed, upon the reveal of the gene drive system earlier this year, researchers have expressed concern about permanently altering wild populations. Among other things, experts worry about the possibility that modified organisms could accidentally escape lab experiments or that they could be made for malicious purposes.

An August editorial in Nature concluded that ”[r]egulators and the wider world need to keep pace with the rapid development of CRISPR technology, and there is little time to waste.” The National Academy of Sciences is currently working on a report on the responsible use of gene drive systems.

Proceedings of the National Academy of Sciences, 2015. DOI: 10.1073/pnas.1521077112

(About DOIs).