A female Anopheles gambiae mosquito. Its red eyes indicate the presence of a modified gene intended to confer malaria resistance
Rebeca Carballar-Lejarazú
Gene editing has been used to create mosquitoes that are resistant to the malaria parasites.
Because the modified mosquitoes have a “gene drive” sequence, their children will be immune to the disease even if they are introduced into a natural mosquito population. Human malaria cases could be drastically reduced by adopting this strategy.
Young children in sub-Saharan Africa are particularly vulnerable to the devastating effects of malaria, which is one of the world’s leading causes of mortality and illness. Two vaccinations have been produced in recent years, but neither provides complete protection.
Gene drives that eradicate all mosquitoes in a specific region are one of the high-tech methods being studied to combat mosquito-borne diseases. However, Anthony James of the University of California, Irvine, warns that these may have unexpected consequences for ecosystems.
Their strategy permits mosquitoes to continue breeding, but eliminates the principal malaria-causing parasite, the one-celled Plasmodium falciparum.
Two antibody fragment genes have been introduced into the mosquito genome; these antibodies are specific to distinct stages of the parasite’s development within the mosquito host. According to James, this makes it less likely that the parasite will develop resistance.
Furthermore, it carries a sequence that indicates it will likely be passed around the population. Because it is programmed to insert itself into an eye colour gene, any genetically modified mosquitoes will have red eyes, making it easier to track their effectiveness.
The eye pigment gene is the sole target of the Cas9 enzyme, which is also utilised in CRISPR-based gene-editing therapies. The DNA also contains a “guide” DNA sequence.
The offspring of a genetically modified mosquito and a non-modified mosquito will initially only pass on one copy of the modified eye pigment gene. Normal DNA repair enzymes take the engineered DNA as a template and copy that sequence into the normal gene after the Cas9 enzyme creates a break in the normal gene. This leaves the offspring with two changed genes.
In laboratory tests, the method was found to be inefficient in the mosquito species Anopheles gambiae because it reduced the males’ fertility. However, the Anopheles coluzzii mosquito population did not show this drawback.
Mosquitoes of this species had fewer parasites than unmodified insects, and the gene transmitted rapidly through small cages of mosquitoes. This led the team to conclude that in ideal conditions, human malaria cases may be reduced by more than 90% within just three months of releasing genetically engineered mosquitoes on an island.
Discussions are currently underway to put the strategy to the test on So Tomé, an island 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,” explains Luke Alphey from the University of York in the UK. Using a different approach, Alphey co-founded Oxitec and the company is releasing mosquitoes infected with bacterium called Wolbachia, which prevents them from spreading dengue virus.
Malaria treatment approaches that don’t destroy the insects may be preferable from an ecological standpoint, according to Sadie Ryan of the University of Florida in Gainesville, because mosquitoes can still play a function in the environment.
FAQs:
Q: How are mosquitoes engineered to resist malaria?
A: Scientists use gene editing to introduce antibody fragment genes into mosquito genomes, reducing their susceptibility to the malaria-causing parasite.
Q: What is a “gene drive” sequence in mosquitoes?
A: A “gene drive” sequence ensures that offspring inherit malaria resistance, even when introduced into natural mosquito populations.
Q: Why is malaria a major concern in sub-Saharan Africa?
A: Malaria is a leading cause of mortality and illness in sub-Saharan Africa, particularly affecting vulnerable young children.
Q: What are the potential benefits of gene-edited mosquitoes for malaria control?
A: Gene-edited mosquitoes could significantly reduce malaria transmission, offering a promising strategy for disease eradication.
Q: Are there any ecological concerns associated with gene-edited mosquitoes?
A: Some experts express concerns about the ecological impact of gene-edited mosquitoes and potential unintended consequences for ecosystems.
