The old joke says that infertility isn't hereditary, but a team of scientists at Imperial College London is proving it wrong as a way to fight malaria. Using gene splicing, the team is working on a way to introduce a strain of infertility into female Anopheles gambiae mosquitoes that can be passed from one generation to the next to significantly cut, if not eradicate, local populations of the malaria-carrying insect.

According to the UNICEF, 300 to 600 million people are infected with malaria, killing one million each year with 90 percent of the cases in sub-Saharan Africa. With such a terrible toll, it's no wonder that finding a way to control its spread is such a high priority.

One major approach has been to break the chain of infection that spreads the disease. Since the main vector is mosquitoes from the Anopheles genus, suppressing their population has proven the most successful way of combating malaria. This usually involves draining standing water or coating it with oil to suffocate the aquatic mosquito larvae, spreading insecticides, using standing nets, and sterilizing mosquitoes using radiation. However, these require major logistical exercises that are very expensive and with insecticides there's always the danger of the insects developing resistance.

Advances in genetic engineering have opened up other potential approaches, such as creating mosquitoes without wings, ones that can't contract malaria, or have impaired smell so they can't bite people. The Imperial College team's approach is to reduce mosquito populations by modifying female Anopheles gambiae so they carry a gene that makes future generations infertile by disrupting egg production.

Unlike other sterilization methods, the Imperial College team's approach, called "gene drive," exploits recessive genes. Basically, each parent contributes 50 percent of the genes to their offspring and which traits appear in the next generation depend on whether the genes are dominant or recessive. With dominant genes, such as those for brown eyes in humans, only one in a gene pair needs to carry it. But with recessive genes, such as for blue eyes, both need to carry it for it to express itself.

According to Imperial College, if the sterility trait was dominant, it wouldn't have much of a chance to spread because it would immediately appear in the next generation and destroy it. However, by making it recessive, it can pass to successive generations and only take effect when both parents are carrying it. The result is that over 90 percent of male and female offspring end up with the gene, offering the potential to drastically reduce, if not completely eradicate local populations of the malaria-carrying species.

The way the team accomplished this was by treating three different fertility genes with CRISPR/Cas9 endonuclease. This DNA-cutting enzyme severed the genes at a specific spot in the genetic code and when the chromosome repaired itself, it used the altered gene introduced by the team as a template. With this level of control, it was possible to ensure that the gene was recessive and by working on several different genes, the chances of the mosquitoes developing any resistance were reduced.

"As with any new technology, there are many more steps we will go through to test and ensure the safety of the approach we are pursuing," says Professor Austin Burt from Imperial's Department of Life Sciences. "It will be at least 10 more years before gene drive malaria mosquitoes could be a working intervention."

Study lead author Dr Tony Nolan points out that Anopheles gambiae is only one of around 800 species of mosquito in Africa, and of around 3,400 species worldwide. As a result, suppressing populations of this malaria-carrying species isn't expected to have a significant impact on the local ecosystem.

The team's results were published in Nature Biotechnology.

Source: Imperial College London