Gene Drives Vs Malaria (+Zika & Dengue) – Will Mosquitoes Survive the Showdown?

What Are Gene Drives?

Gene drives build upon CRISPR technology, (like a CRISPR 2.0), to actively target and replace detrimental genetic traits present in the genome.

Unlike CRISPR, gene drives can be used to replace both alleles of a gene in an organism as they also include the code for an endonuclease; an enzyme capable of cutting out faulty versions of the gene on either chromosome. After removal of the faulty alleles, the cell is able to repair itself using the inserted gene as a template for both alleles. As a result, all offspring will inherit and express the characteristics of the newly inserted gene.

Note: Don’t try this on bacteria or viruses – it won’t work! Gene Drives only function correctly in sexually reproductive organisms.

Gene drives could, therefore, be used to eliminate diseases such as malaria and Lyme disease. In the case of malaria, mosquitoes could be modified to increase their resistance against the protozoan parasite. In time, all mosquitoes would be resistant; effectively removing malaria’s main transmission vector.

However, there are many risks to consider before releasing this technology into the environment. Risk Bites explains both the staggering theoretical rewards and the potential doomsday-like risks of using gene drives.

Gene Drives: The Nemesis of Mosquito-Borne Disease?

Gene Drives could leave the likes of Malaria, Zika, and Dengue nowhere to hide by either sterilizing mosquitoes so that they produce non-viable offspring or by providing the mosquitoes with virus-resistant genes. Both of these options would remove the vital reservoir and transmission vector for all three mosquito-borne diseases, leaving them looking for alternative transportation! No more free bus passes!

There is good reason researchers are excited about gene drives. They could prevent hundreds of thousands of deaths and worldwide suffering. Here are some shocking stats about the terrible suffering caused by these diseases and their main transmission vectors.

Malaria

In 2016 there were around 216 million cases of malaria in 91 countries, with 445,000 deaths worldwide. On top of that, there are 3 billion people living in areas where they are frequently at risk of contracting malaria. Anopheles stephensi is the main carrier of malaria in Asia, while Anopheles gambiae is a major carrier is of malaria in sub-Saharan Africa.

When bitten by the mosquito, humans are infected by the Plasmodium (malaria) parasite. The Plasmodia migrate to the liver cells and multiply in number. Unfortunately, the sturdy parasite doesn’t stop there, next on its target list are the host’s red blood cells (erythrocytes). Here the malaria parasite continues to multiply until the blood cell bursts, releasing daughter parasites called merozoites which can potentially continue infection until patient death. If another mosquito bites the infected host, the malaria parasite can hitch a ride and continue the cycle of misery.

In the video below, Kurzgesagt uses their usual beautiful animations to explain how gene drives could defeat this monstrous disease once and for all.

Zika Virus and Dengue Fever

Zika has had global attention recently due to a large outbreak in Brazil in 2015, with symptoms reportedly including Guillain-Barré Syndrome and microcephaly. Aedes Mosquitoes, (usually Aedes aegypti), are responsible for spreading Zika.

Dengue Fever causes around 390 million infections each year, with around 40% of the global population at risk. Aedes aegypti mosquito is the main vector.

Option 1: Sterilize Mosquitoes/Non-viable Offspring

Mosquitoes that are known to carry viruses such as Zika or malaria could have their genome edited so that any offspring they produce are unable to survive or are sterile upon birth. This could potentially wipe out the disease-transmitting species, and so remove the disease reservoir and transmission vector entirely. A little unfair on the mosquitoes as the diseases they transmit are usually not beneficial for them either, but a viable option to remove crucial transmission vectors.

In one example, a team at Imperial College was able to develop sterile female Anopheles gambiae by modifying genes responsible for embryo development and egg formation, thus preventing females from laying any eggs or producing eggs which do not hatch.

Option 2: Add Virus-Resistant Genes to the Mosquitoes

It is also possible to edit mosquitoes in a way that improves their immunity against deadly viruses. Such immunity would preserve the species survival while also improving the health of both humans and mosquitoes.

In one research lab at the University of California, a team inserted malaria-blocking genes into Anopheles stephensi mosquitoes, via the CRISPR-Cas9 system. The genes code for two antibodies specifically targeting Plasmodium (which malaria is a parasite of).

Concerns

There are concerns that newly inserted genes could be picked up by other organisms via lateral gene transfer, possibly causing damage to the wider environment. The new gene could also have unknown effects on the rest of the organism’s genome, and once gene drives are released into the environment their effects will be very hard to undo if something goes wrong.

As responsible scientists, researchers in this field continue to carry out thorough testing and research on this technology before letting the gene drive out of the lab.

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