MALARIA: genetic alteration of mosquitoes

Michael Riehle is holding a container full of mosquitoes. But he doesn’t necessarily want the insects to die. He wants them to live long enough, so he can open up their guts and count the number of parasites they have.
Gross? Well, yes. But it’s also a discovery that could wage a war against malaria through the use of genetically engineered mosquitoes. In recent experiments, a University of Arizona entomologist Riehle isn’t finding any parasites in the mosquitoes designed to be resistant to malaria.

Eliminating human malaria from a mosquito was exactly what Riehle, had been trying to achieve for the last three years.
Riehle put a gene in a mosquito to over-express a gene that was already there, which converted the gene into an active state.
The mosquito’s gene, Akt, is involved in a number of processes, including lifespan, digestion, and reproduction. Therefore, it takes 3 to 4 months to create a genetically engineered mosquito that is completely immune to the parasite that causes malaria.
“I think it’s a pretty big step forward. We’ve completely blocked the development of the human malaria parasite in the mosquito. Previous research has not completely blocked it,” says Riehle.
The other groups achieved up to 97 percent, but 100 percent is essential if the goal is to control it on the field.
When a mosquito transmits malaria, it injects about 40 sporozoites from its gut. From there, the parasite makes its way to the mosquito’s salivary glands, where it can infect an unsuspecting person. Unfortunately, it only takes one parasite to cause malaria.
“Even if a single parasite survives to form a oocyst, then the mosquito will be able to transmit malaria. If the parasite can avoid the killing mechanism, resistance will develop and the mosquito will no longer be effective,’ Riehle says.
Riehle’s experiment looked at two types of mosquitoes — one was a control (or the wild type) and the other one was a transgenic breed. After the insects are feed infected blood meal, the mosquitoes are left to develop for 8 to 10 days. That’s when the researchers dissected the guts and counted the number of parasites.
“We saw nice infections in the control and not a single parasite in the genetically engineered ones,” Riehle says.
“This work is really exciting because the authors completely eliminated malaria infection by over-expressing just a single gene in the mosquito,” University of Notre Dame malaria postdoctoral researcher Bradley White says. “Moreover, the same transgenic mosquitoes had shorter life spans, which could also yield decreases in malaria transmission since only relatively old mosquitoes transmit the parasite.”
Riehle knows that, admitting “the biggest hurdle is to drive them into the wild population. They have a shorter lifespan, so they wouldn’t compete [with the others]. Even if you released a few million mosquitoes, they would be out competed by the wild mosquitoes and just disappear.”
That’s not the only hurdle.
The mosquito species studied, Anopheles stephensi, is a major vector of malaria in parts of Asia, but it is not one of the major vectors in Africa where the vast majority of the world’s malaria-related deaths occur. “Unfortunately, the major African vectors remain unnameable to transgenesis — the technique used in this study — although research in overcoming this obstacle is ongoing in many labs,” White says.
However, Riehle thinks the method should work in the main African vector. “They will be able to reproduce with the wild mosquitoes. They won’t produce as many eggs, but that can be overcome by giving them a competitive fix,” he says.

Until designer mosquitoes are unleashed into the wild, there’s always insecticide-laced nets that can do the job.
But then again, not everyone is even using them in Africa.
“Insecticide-treated bed nets, or drugs to cure the malaria are effective ways [to prevent malaria], except resistance is developing against the parasites,” Riehle says.
Give the genetically engineered mosquitoes 10 years to emerge as a viable solution to the fight against malaria. This will only happen if the mosquitoes can compete with the disease-ridden wild ones.
Still, there’s a lot more work to be done in the lab before these mosquitoes are fit enough to infiltrate the wild population. “At this point, we don’t know the exact mechanism of how the parasites are being killed,” Riehle says.