Extinguishing malaria with genetic engineering

Imagine that it was possible to genetically modify an organism so that the species to which it belongs disappeared? Or imagine it was possible to genetically modify a population of an endangered species in such a way as to preserve it? Well, it is possible and we will explain how and why.

Gene drive is a genetic engineering technique that theoretically allows 100% of a gene to be transmitted by sexual reproduction. Using the CRISPR/Cas9 genome editing technique, gene drives offer the possibility of modifying a whole species and opens up a wide range of solutions to address global issues.

This technique can be useful in particular for controlling invasive species, for removing undesirable genes, such as genes associated with resistance to antibiotics or insecticides, and it can be useful for reducing the spread of certain species. In short, the fields of application are as follows: agriculture, disease control, conservation and biological weapons, for example to transmit certain pathogens more effectively.

But how, you may ask, can a new gene be introduced or deleted? To do this, we use the CRISPR-Cas9 method which acts like molecular scissors and allows us to cut a gene at a specific location and introduce a mutation there.

This is how it is done. First, scientists have to manufacture a particular RNA which recognizes a specific place on the DNA where we want to make the insertion. Then, The guide RNA associates with the Cas9 and the two form a “molecular scissor”, allowing the cut at the desired location. This damages the DNA. In this way, the cell will carry out a repair by introducing a mutation randomly.

However, gene drive is not perfect because it is an irreversible and uncontrollable method. Normally, the genomic modification carried by the mother should be transmitted only to half of the offspring, but thanks to gene drives, we guarantee a copy of this modification in the paternal chromosome. Thus, the progeny carry two copies of the modification which is found in the homozygous state. 

The image above shows how this is done. A green DNA fragment is a modified gene that will spread to the whole population. The image shows how Cas9 inserts the modified gene so that both chromosomes have it.

Indeed, once the genetically modified individuals are released there is no turning back and the transmission is almost certain for all the descendants. It is a chain reaction at the end of which all the individuals of a population are carriers of the trait resulting from the gene drive.

The case of malaria

Malaria is an infectious disease caused by a parasite of the genus Plasmodium. The latter have the particularity of using several hosts during their development cycle.

The life cycle of the malaria parasite involves two hosts: the mosquito first, and humans second. The mosquito will host the plasmodium in its salivary glands which it will transmit by picking when the insect bites a human or another vertebrate.

It is estimated that this disease affects 250 million people, of whom 900,000 die each year. Due to its prevalence and the lack of effective treatments and vaccines, malaria is still a major public health issue in 2022. To counter this, many scientists are trying to fight this disease using genetic engineering and gene drives.

The battle with malaria

Well then, how can we use this new and powerful technique to combat malaria? Can we in fact eradicate the disease completely? The truth is that we probably can (1). Yet gene drives have not yet been used for eradicating malaria. The technique is too powerful, it is still too dangerous to let gene drives run free in the wild. Gene drives will probably be used sometime in the future though, so let us examine two methods for eradicating malaria!

One of the methods is population suppression. A gene drive can be used to make female mosquitos infertile, which could eradicate or significantly decrease the population of a mosquito species. The gene drive will still spread as male mosquitos continue to mate and have offspring. It is worth mentioning that not all mosquito species can carry malaria, and not all malaria carrying species can carry types of malaria that affect humans. One mosquito species that is especially dangerous is Anopheles gambiae, which can carry the most dangerous malaria parasite, Plasmodium falciparum. If we could just get rid of Anopheles gambiae, that would be great for reducing malaria. But eradicating an entire species is dangerous, it could have a significant role in the ecosystem. There is an ongoing debate about this. Malaria carrying species could perhaps be replaced by other mosquitos. There is however a risk for other disease carrying species to take over (2)!

There is also another technique to combat malaria with gene drives. Through gene editing techniques, scientists have managed to make mosquitoes malaria resistant. Those mosquitos are still of the same species that can carry malaria. Now all we need is to make the malaria resistant mosquitos transfer their genes to the whole population! This could also be accomplished with gene drives, and is called population replacement. The picture below shows how this would look like. The modified green mosquitos in the picture take over within a few generations.

Wrapping Up

Let us take a moment to look back and see what we have learned in this post. First we have gene drives. The CRISPR/Cas9 method makes it possible to cut and paste genes. This is used to make an organism have a modified gene in each chromosome, which leads to the gene being transmitted to all offspring. This can be used to combat malaria. Malaria is caused by a virus that is transmitted to humans by mosquitoes, and causes the death of approximately 900,000 people each year. We have also seen that there are actually two ways to combat malaria with gene drives. One way is population suppression, which means you eradicate or significantly decrease the population of a species. The other way is population replacement, where a whole species is modified. In conclusion, we have examined everything regarding combating Malaria with gene drives.

Hopefully nothing will go wrong if we choose to use this ridiculously powerful new technique called gene drives. But in the best case scenario, we might in the near future witness the historical moment when the disastrous disease malaria is eradicated.

We hope you found our article interesting, and thank you for reading! Stay tuned for future articles!

References

  1. Jennifer Kahn, 2016, “Gene editing can now change an entire species — forever | Jennifer Kahn”
  2. Hayley Dunning, 2021, “Malarial mosquitoes suppressed in experiments that mimic natural environments”
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Salomé Ifergan
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