Malaria and Zika: CRISPR gene editing could wipe out blood-sucking female mosquitoes

CRISPR gene editing techniques have the potential to edit out blood-sucking female mosquitoes, potentially providing an avenue through which to curb diseases like malaria, Zika and dengue. Scientists say the recent discovery of what makes male mosquitoes male coupled with gene editing techniques would enable them to edit out the female genes.

This idea works on the basis that female mosquitoes are the ones that bite people as they need to feed on blood to produce eggs. Males, on the other hand, feed on nectar so do not spread disease.

Zach Adelman and Zhijian Tu from Virginia Tech highlighted the possibility of getting rid of female mosquitoes in a review article for the Cell Press journal Trends in Parasitology. The article forms part of a special issue on vectors.

"Anopheles mosquitoes are the primary vectors of malaria, one of the most deadly and costly diseases in human history. Aedes aegypti is a major vector for dengue, yellow fever, and chikungunya viruses. ... More recently, similar factors have led to the large-scale emergence of viruses such as chikungunya and Zika, both also vectored by Ae. aegypti. Current prevention of these mosquito-borne infectious diseases depends heavily on effective vector control, which is hindered by increasing insecticide resistance."

They said that recent work into releasing sterile male mosquitoes has successfully reduce local populations of the mosquito that spreads dengue. However, this approach is not ideal because of challenges relating to scalability, as well as separating the sexes before they are released.

Recent breakthroughs in two fields of research, could, however, be brought together to address the large-scale control of mosquito populations. In a study published last year, Adelman and Tu announced the discovery of the first male-determining factor in mosquitoes. Expression of a sex-determination gene called Nix caused female embryos to develop external and internal male genitalia.

In separate research, breakthroughs are being made in CRISPR-Cas9 gene editing technology. It has already been shown to work in the Asian malaria vector An. Stephensi so that for several generations, males containing the gene drive produced almost no transgenic offspring. "While the effectiveness and long-term stability of CRISPR-based gene drive constructs in mosquitoes remains unknown, these results are highly encouraging," they wrote.

However, the scientists say their findings coupled with gene editing could be used to edit out females altogether. "Given recent breakthroughs in the development of CRISPRCas9 reagents as a source of gene drive, more advanced technologies at driving maleness, the ultimate disease refractory phenotype, become possible and may represent efficient and self-limiting methods to control mosquito populations," they said.

Adelman said we are currently at a "turning point" in our understanding of both how mosquitoes become male or female and how we can used gene drive techniques to control populations. These areas have the potential to provide promising pathways through which to curb the spread of dengue, malaria, Zika and yellow fever.

"This discovery sets the stage for future efforts to leverage the CRISPR-Cas9 system to drive maleness genes such as Nix into mosquito populations, thereby converting females into males or simply killing females," Tu said. "Either outcome would help to reduce mosquito populations and improve sex separation procedures, which are required in any genetic strategy to prevent the accidental release of disease-transmitting females into wild populations."

They said far more research is needed to work out how to apply the technique, while the long-term stability of CRISPR-based gene drive systems is not yet known. Ethical implications are also highlighted – if any experimental mosquitoes escaped, there could be unknown consequences. "Moving forward, partnerships with supportive governments, local collaborators and a willing public will be crucial to establishing field-based testing in areas that are most impacted by mosquito-borne diseases," Adelman said.