A new approach to gene drives: combining suppression and modification drives for malaria control

Blog post by Dr. Sebald Verkuijl

This World Malaria Day, the Transmission Zero team had a new paper published in Nature Communications describing an exciting new gene drive mosquito concept with huge potential for malaria control.

Malaria remains a devastating global health challenge, responsible for hundreds of thousands of deaths annually. In 2023, the World Health Organisation reported an estimated 263 million malaria cases and 597,000 deaths globally. Sub-Saharan Africa bears the majority of the disease burden, with most deaths being among children under 5.

Alarmingly, progress towards malaria elimination has stalled in recent years, largely due to increasing drug and insecticide resistance, whilst new challenges, including climate change and inconsistent funding, threaten further progress. Therefore, it is essential to develop new and innovative tools to tackle this disease.

At Transmission Zero, researchers are working to develop new genetic tools that prevent mosquitoes from transmitting the malaria-causing Plasmodium parasites to humans. This approach hinges on efficiently spreading these anti-malarial traits throughout a mosquito population, using something called a gene drive, ensuring all offspring inherit the specified gene.

The new paper, titled ‘A suppression-modification gene drive for malaria control targeting the ultra-conserved RNA gene mir-184’ showcases a novel approach that combines two proposed concepts for malaria control gene drives: population suppression, combined with a modification strategy designed to overcome resistance.

The study presents a highly efficient gene drive that targets a non-coding micro-RNA gene called mir-184. This target site is conserved across many mosquito species, including Anopheles gambiae, a key African malaria vector, which was successfully targeted in this research.

As well as being highly conserved across mosquito species, the miR-184 RNA is highly expressed within mosquitoes, particularly in female midguts following a blood meal. The mir-184 gene is a particularly attractive target site, because as a non-protein coding gene, it is expected that incorrect DNA repair events are less likely to generate functional resistance alleles to the gene drive.

Beyond this, the study demonstrated that gene drives targeting mir-184 are inherited across both sexes with high efficiency and, importantly, the gene drive can propagate itself and the anti-malarial effector gene within caged mosquito populations.

Interestingly, disruption of the microRNA by the gene drive also reduces mosquito lifespan and interferes with survival after females take a blood meal, hence also exhibiting population suppression features. Modelling indicates that the intermediate effects on vector survival could be highly effective in reducing malaria transmission.

The team are delighted to share this development as a significant step forward in gene drive research.

To read more about this exciting development, please check out the paper here: https://bit.ly/4iGe654