Monday, September 25, 2023

Malaria-immune mosquitoes could help end the disease -Dlight News

Mosquitoes have been genetically edited to be immune to the parasites that cause malaria.

If released into the wild, the genetic modification should spread through a mosquito population because it contains a sequence known as a “gene drive,” meaning that all offspring of the modified insects would inherit immunity. This approach could drastically reduce the number of malaria cases in people.

Malaria is one of the world’s leading causes of death and ill-health, exacting 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 investigated, including gene drives that kill all mosquitoes in a specific area. But these could have unpredictable effects on ecosystems, he 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 parasite that causes malaria, a single-celled organism called Plasmodium falciparum.

The inserted DNA includes the genes for two antibody fragments; each targets the parasite at a different stage in its life cycle within mosquitoes. This reduces the chance that the parasite will develop resistance, says James.

It also carries a sequence which means it should spread through the population. It is designed to be inserted into a gene. for eye color, which means that any modified mosquito has red eyes, which helps control the success of the strategy.

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 and one normal eye pigment gene. But the Cas9 enzyme makes a break in the normal gene, then the usual DNA repair enzymes use the modified DNA as a template and copy that sequence into the normal gene, so the offspring results in two modified genes.

When tested in the laboratory, the system proved ineffective on a species of mosquito, called Anopheles gambiae, because it made males less successful at mating. But this disadvantage was not seen in another species of mosquito called Anopheles coluzzii.

In this species, the gene spread rapidly through small mosquito cages, and as a result, they harbored fewer parasites than undisturbed insects. Based on this, the team calculated that if modified mosquitoes were released on an island, under optimal conditions, human cases of malaria could be reduced by more than 90 percent in 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 one of the main causes of malaria.

“They’ve put together a pretty good anti-pathogen effector and a pretty good gene drive in one package,” he says. Lucas Alphey at the University of York, UK. Alphey co-founded a firm called oxitec that he is using a different technique, releasing mosquitoes infected with a bacterium called wolbachianthat it cannot spread the dengue virus.

sadie ryan at the University of Florida in Gainesville says malaria control methods that don’t eradicate insects might be better from an ecological perspective, since mosquitoes can still play a role in the ecosystem.

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