CRISPR-Based Gene Drive Technology in Mosquitoes

Author: Soumyadeep Talukdar

ABSTRACT
Malaria, according to the CDC, is “A mosquito-borne disease caused by a parasite. People with malaria often experience fever, chills, and flu-like illness.” Without treatment, those who are infected with malaria meet their end. Around 229 million cases of malaria occurred around the globe in 2019, with around 409,000 deaths. The majority of the victims come from Africa and are children. With an urgent need of finding a way to combat this disease, scientists are looking at the method of using genetic engineering. This article goes over some of the ways scientists hope to use genetic engineering in order to reduce the number of malaria cases.
INTRODUCTION
Malaria is caused by a parasite known as Plasmodium, which only a select few mosquitoes carry in their guts. As the years go by, mosquitos are becoming more and more resistant to pesticides. The parasite causing malaria has also been becoming resistant to antimalarial drugs. With the amount of cases rising and heavily concentrated in Africa, scientists are using genetic engineering to reduce the malaria infected population.
GENE DRIVES APPROACH
Currently, CRISPR-based gene drive technology is being tested as a new approach. By creating and releasing genetically altered mosquitoes into the environment, they would spread genes to heavily diminish mosquito populations in a specific area or decrease the chances of malaria spreading amongst mosquitoes.

Figure 1 – Red mosquitoes represent mosquitoes with a modified gene

Figure 2 – Red mosquitoes represent mosquitoes with modified genes and gene drive. Compared to Figure 1, almost all of the offspring inherit the modified genes, showing the effectiveness of gene drives in stopping malaria.
The team genetically altered Anopheles Gambiae mosquitoes. After the mosquitoes feed on blood, they express small antimicrobial molecules. These molecules target and weaken the Plasmodium parasite’s development. The team also tested whether the genetically modified mosquitoes could successfully reproduce, the difference in development of malaria parasites in the mosquito’s guts, and if the mosquitoes remained healthy. The results of their experiments showed positive results, which also serve as evidence that these genetic alterations are able to create successful gene drives.
Previous attempts at using gene drives were only partially successful. Over time, mosquitoes began developing a resistance to the altered gene. In other words, mutations appeared which negated the effectiveness of the altered genes which stopped their spread.
However, researchers may have found a way to get past this dilemma. They focused on targeting a gene responsible for determining the gender of a mosquito called ‘doublesex.’ Male mosquitoes with the altered gene are able to develop normally. Female mosquitoes, however, were unable to produce eggs if they had two copies of the gene. To prove this methodology, researchers tested how well this gene spread throughout mosquito generations. They found out that after 7 to 11 generations, every mosquito carried the altered gene. Thus, the malaria infected mosquito population collapsed.
CONCLUSION
Although their experiments shared positive results, it does not mean that they can start using it on populations in the wild just yet. More tests are needed to be run, such as the effects of gene drive in larger confined spaces with conditions that replicate real conditions of the environment. We shouldn’t disregard the chance that mosquitoes can develop yet another resistance to this method.
Speculations aside, this is one major step to lowering malaria cases around the globe. The discovery yielded by this experiment is one to advance genetic engineering in mosquitoes in the future.
SOURCES

1. Berthold, Emma. “Malaria-Carrying Mosquitoes Shut down with Gene Drive.” Science.org, Australian Academy of Science, 24 May 2021, www.science.org.au/curious/people-medicine/malaria-carrying-mosquitoes-shut-down-gene-drive.
2. Dunning, Hayley. “Simple Genetic Modification Aims to Stop Mosquitoes SPREADING Malaria: IMPERIAL News: Imperial College London.” Imperial News, Imperial College London, 13 Apr. 2021, www.imperial.ac.uk/news/219394/simple-genetic-modification-aims-stop-mosquitoes/.
3. CDC. “CDC – Malaria – Malaria Worldwide – How Can Malaria Cases and Deaths Be Reduced? – Drug Resistance in the Malaria Endemic World.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 23 July 2018, www.cdc.gov/malaria/malaria_worldwide/reduction/drug_resistance.html.
4. CDC. “CDC – Parasites – Malaria.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 30 June 2021, www.cdc.gov/parasites/malaria/index.html.
5. Geddes, Linda. “Genetic Engineering Test with Mosquitoes \’May Be Game Changer\’ in Eliminating Malaria.” The Guardian, Guardian News and Media, 28 July 2021, www.theguardian.com/world/2021/jul/28/genetic-engineering-test-with-mosquitoes-may-be-game-changer-in-eliminating-malaria.

FIGURE SOURCES
Figures 1 and 2 – Berthold, Emma. “Malaria-Carrying Mosquitoes Shut down with Gene Drive.” Science.org, Australian Academy of Science, 24 May 2021, www.science.org.au/curious/people-medicine/malaria-carrying-mosquitoes-shut-down-gene-drive.
IMAGE SOURCES
Article Image – Natalie Kofler Scientific Citizenship Initiative Advisor and Center for Bioethics Lecturer, et al. “Genetically Modifying Mosquitoes to Control the Spread of Disease Carries Unknown Risks.” The Conversation, The Conversation, 8 July 2021, www.theconversation.com/genetically-modifying-mosquitoes-to-control-the-spread-of-disease-carries-unknown-risks-123862.