Could CRISPR help wipe out mosquito-borne diseases?

New Trends in Parasitology study says the gene editing tool could be used to remove blood-sucking female mosquitoes from the population.

The study, published today, highlights how CRISPR could be used to stop the spread of deadly diseases such as malaria, Zika, and yellow fever by manipulating the sex selection process in certain species of mosquitoes. We speak to the study’s two lead authors, Zach Adelman and Zhijian Tu, both entomologists at Virginia Tech University, to find out more.

RG: Can you explain the role CRISPR could play in stopping the spread of disease via mosquitoes?

Zhijian Tu: Only female mosquitoes bite and suck blood, and hence are responsible for spreading disease amongst humans, males feed purely on nectar. We recently discovered the sex-determination gene in mosquitoes – called the Nix gene. Combining this knowledge with the CRISPR-Cas9 gene editing tool, we could bias mosquito populations towards being male, hence contributing to the control of mosquito-borne diseases such as dengue fever, malaria, yellow fever and Zika.

RG: What is the state of research into how CRISPR could be used to engineer a male-dominated mosquito population?

Zach Adelman: We are still at the beginning of the research. There are a lot of questions that need to be answered – we don’t yet know, for example, what the effectiveness and long-term stability of CRISPR-based gene drive systems in mosquitoes are.

RG: If certain species of mosquitoes do die out, what effect could this have on the ecosystem? Would it be possible for a ‘worse’ species to take over instead?

Tu: There are more than three thousand species of mosquitoes and only a very small fraction of them transmit disease-causing pathogens to humans. We are only interested in reducing the populations of these mosquito species. If we take the Aedes aegypti species as an example, it is an invasive species in many parts of world where the dengue and Zika diseases are a problem. In other words, Aedes aegypti exist in these areas largely as a result of globalization.

Additionally, the vector for dengue and Zika viruses are highly adapted to human environments and are, to a certain extent, a "domesticated" species. Finally, the genetic method we are developing is species-specific by definition as it requires mating. In this sense, it is eco-friendly as it should have minimal impact on other non-target species.

: Again, it depends greatly on the target species. For an efficient, invasive vector like Aedes aegypti, there is nothing like it on Earth, and certainly nothing worse that could potentially take its place.

RG: What are the potential risks of implementing this research?

Tu: There are some concerns and risks of implementing this research. For example, accidentally releasing just a few of these mosquitoes during testing could be sufficient to establish gene drive systems in the wild, and it is not yet clear how to remove an introduced gene from a study area if needed. As the ethical and regulatory guidelines have not yet been established, The National Academies of Sciences, Engineering, and Medicine is currently developing recommendations for the responsible conduct of gene drive research in non-human organisms. Having said that, I would emphasize that that the approach we are proposing would ultimately be self-limiting as local mosquito population crash due to insufficient females could eliminate the engineered Nix gene from the environment.

RG: Gene editing is a very controversial topic, have you received any backlash in response to your research?

Adelman: No. But so far, and for the immediate future, our experiments are restricted to the laboratory under confined conditions. In the future, we’d seek to apply this approach in areas around the world where the burden of disease is high and hasn’t been managed by other control methods. However, we’d need the support of governments, local collaborators, and the public in order to field test the research.

RG: What’s the next step in this research?

Adelman: Laboratory experiments still need to be completed to better understand how well the technology works and how it can be controlled in order to inform the safe and responsible conduct of any future field-based trials.

Tu: We are focusing on two main goals. The first is to better understand the molecular mechanism of sex-determination in mosquitoes. The second is to work towards a genetic strategy to effectively reduce mosquito populations by the introduction of bias towards the non-biting males.

ResearchGate has put together a comprehensive collection of emerging Zika virus research, including scientific papers, interviews with researchers, and discussions among them. 

Featured image courtesy of Nathanael Coyne.