A female Anopheles gambiae mosquito. Its red eyes indicate the presence of a modified gene intended to confer malaria resistance
Rebeca Carballar-Lejarazú
Mosquitoes have been gene edited so they are immune to the parasites that cause malaria.
If released into the wild, the genetic modification should spread through a population of mosquitoes because it contains a sequence known as a “gene drive”, which means all the modified insects’ offspring would inherit the immunity. This approach could slash the numbers of malaria cases in people.
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 under investigation, including gene drives that kill all mosquitoes in a targeted area. But these could have unpredictable effects on ecosystems, says Anthony James at the University of California, Irvine.
His team’s approach allows mosquitoes to live, but makes them produce antibodies that kill the major malaria-causing parasite, a single-celled organism called Plasmodium falciparum.
The inserted DNA includes the genes for two antibody fragments; each one targets the parasite at a different stage of its life cycle within mosquitoes. This lowers the chance that the parasite will evolve resistance, says James.
It also carries a sequence that means it should spread through the population. It is designed to insert itself into a gene for eye colour, meaning that any modified mosquitoes have red eyes, which helps in monitoring the strategy’s success.
The DNA encodes 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 will initially have one modified eye pigment gene and one normal one. But the Cas9 enzyme makes a break in the normal gene, then the usual DNA repair enzymes use the engineered DNA as a template and copy that sequence into the normal gene – so the offspring have two modified genes as a result.
When tested in the lab, the system was ineffective in one species of mosquito, called Anopheles gambiae, because it made the males less successful at mating. But this downside wasn’t seen in another mosquito species called Anopheles coluzzii.
In this species, the gene quickly spread through small cages of mosquitoes and, as a result, they harboured fewer parasites than unaltered insects. Based on this, the team calculated that if modified mosquitoes were released on an island, under optimum conditions, human cases of malaria could be cut by more than 90 per cent 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 have put together a pretty good anti-pathogen effector and a pretty good gene drive into a single package,” says Luke Alphey at the University of York, UK. Alphey co-founded a firm called Oxitec that is using a different technique, releasing mosquitoes infected with bacteria called Wolbachia, which can’t spread dengue virus.
Sadie Ryan at the University of Florida in Gainesville says malaria control methods that don’t eradicate the insects could be better from an ecological perspective, as the mosquitoes can still play a role in the ecosystem.
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