An Anopheles gambiae mosquito feeding. Everett Historical/Shutterstock

If you’ve been keeping up with science news, you may well be sick of hearing about CRISPR, the increasingly popular gene-editing tool that keeps making headlines. Well, scientists may have just made another significant breakthrough with this technology: making malaria-carrying mosquitoes sterile.

If these genetic modifications can sufficiently spread through the population, the technique has the potential to reduce mosquito numbers to a level that can no longer sustain malaria transmission. With some of our armamentarium waning in effectiveness, for example due to resistance, this could be a welcome addition to the fight against a global health problem that claims around half a million deaths annually. The study has been published in Nature Biotechnology.

If you are experiencing déjà vu reading this, it’s possibly because you heard a similar story a few weeks ago. Scientists recently published a paper describing the use of CRISPR on mosquitoes, but they went for a slightly different approach, targeting the malaria parasite rather than the insect host. That team managed to successfully use these “molecular scissors” to insert anti-parasite genes into a species called Anopheles stephensi, which plays a major role in malaria transmission in India.

This time round, scientists from Imperial College London used the same system, albeit in a different way, to target the species Anopheles gambiae, the main malaria vector. First off, they began disrupting genes they thought would negatively affect fertility in the females and then assessed effects in the resulting insects. This led the team to three different genes which all conferred sterility in females; however, the mutations they created were only recessive, allowing for the normal development of the female, which is crucial is you want the gene to be propagated in a population.

Malaria parasites bursting out of a red blood cell. Kateryna Kon/Shutterstock

Normally, if a gene is recessive, two genes are required for the characteristic, or phenotype, to show up. So what the researchers did was use CRISPR to function as what is called a “gene drive” system to accelerate the spread of the desirable trait through the population. They inserted gene sequences that coded for cutting enzymes, which snip DNA at a very precise location, in this case the three genes that render the females infertile when mutated.

Here is the really clever part: when these sequences come into contact with a chromosome that doesn’t carry the gene variant, the snipping enzyme comes along and cuts the target sequence along this unaffected strand. This results in a DNA break that’s usually repaired using the variant as a template, meaning that the mutation actually gets copied into what was an un-mutated chromosome. Using this technique, the researchers reported transmission rates of up to 99.6 percent in offspring.

Ultimately, implementation of such a strategy has the potential to reduce populations to such a level that transmission of the disease is no longer supported. And given the number of mosquito species in existence, the ecological impacts should be negligible. As lead researcher Dr Tony Nolan from Imperial explains in a statement: “There are roughly 3,400 different species of mosquitoes worldwide, and while Anopheles gambiae is an important carrier of malaria, it is only one of around 800 species of mosquito in Africa, so suppressing it in certain areas should not significantly impact the local ecosystem.”

There is more work to be done, and rigorous safety assessments will have to be conducted before field trials can be considered, but it’s encouraging to see developments that could ultimately reduce our dependence on things like insecticides. 

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