A female Anopheles gambiae mosquito. Its red eyes indicate the presence of a modified gene intended to confer malaria resistance
Rebeca Carballar-Lejarazu
Mosquitoes are gene-edited so that they are immune to the parasites that cause malaria.
If the genetic modification is released into the wild, it should spread through a population of mosquitoes because it contains a sequence known as a “gene drive,” meaning that all offspring of the modified insects would inherit the immunity. This approach could reduce the number of malaria cases in humans.
Malaria is one of the world’s leading causes of death and ill health, taking a particular toll on young children in sub-Saharan Africa. Two vaccines have recently been developed, but they only give partial immunity.
Other high-tech strategies against mosquito-borne diseases are being explored, including gene drives that kill all mosquitoes in a given area. But these can have unpredictable effects on ecosystems, says Anthony James at the University of California, Irvine.
His team’s approach allows mosquitoes to live but causes them to produce antibodies that kill the main malaria-causing parasite, a single-celled organism called Plasmodium falciparum.
The inserted DNA contains the genes for two antibody fragments; each targets the parasite at a different stage of its life cycle within mosquitoes. This reduces the chance of the parasite developing resistance, says James.
It also has an order that means it must spread through the population. It is designed to insert itself into a gene for eye color, which means that each modified mosquito has red eyes, which helps monitor the success of the strategy.
The DNA codes for an enzyme called Cas9 — also used in CRISPR-based gene-editing therapies — along with a “guide” DNA sequence that means the enzyme only targets the eye pigment gene.
The offspring of a modified mosquito and a normal mosquito initially have one modified eye pigment gene and one normal gene. But the Cas9 enzyme makes a break in the normal gene, and then the usual DNA repair enzymes use the manipulated DNA as a template and copy that sequence into the normal gene, resulting in two modified genes in the offspring.
When tested in the lab, the system was ineffective on one species of mosquito, called mosquitoes Anopheles gambiae, because it made the males less successful at mating. But this disadvantage was not seen in another mosquito species called Anopheles coluzzii.
In this species, the gene spread quickly through small cages of mosquitoes, harboring fewer parasites than unmodified insects. Based on this, the team calculated that if modified mosquitoes were released onto an island, under optimal conditions, human malaria cases could be reduced by more than 90 percent within 3 months.
The researchers are now in talks to test the approach on the island of São Tomé, off the west coast of Africa, where A. coluzzii mosquitoes are a major cause of malaria.
“They’ve put together a pretty good anti-pathogenic effector and a pretty good gene drive in one package,” he says Luke Alphey at the University of York, UK. Alphey co-founded a firm called Oxitec that is with a different technique, the release of bacteria-infected mosquitoes Wolbachiathat cannot spread the dengue virus.
Sadie Ryan at the University of Florida in Gainesville says malaria control methods that don’t eradicate the bugs may be better from an ecological perspective, since the mosquitoes can still play a role in the ecosystem.
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