Gene editing: CRISPR/cas9's role in combating malaria

March 6, 2019

With climate change warming the planet, mosquitoes have hitched the heat wave and are invading throughout the planet.[1] And with mosquitoes, come the most unwelcome of guests - the parasite plasmodium malariae.

 

Plasmodium malariae is a parasite responsible for causing malaria. These parasites invade our liver and blood cells, multiply inside of them, burst into our blood vessels, and hitch a ride on a mosquito to find its next victim.[2]

 

Current methods to fight off malaria are conventional methods, such as the usage of pesticides to kill off mosquitoes, or medicine to fight off the parasite plasmodium malariae. These methods only manage to stem the tide of malaria, but causes tremendous economic and environmental costs in the process.[3][4] Not only that, the CDC reports that in some regions of the world, plasmodium malariae started to develop resistance against conventional medicine such as chloroquine and quinine[5], signalling a growing public health crisis.

 

However, this isn’t a doom-and-gloom news calling for the end of humanity. Thankfully, humans have made plans of their own.

 

Introducing the newest weapon in its arsenal - the CRISPR/cas9 system.

 

Cas9, otherwise known as CRISPR associated protein 9, is an enzyme that cuts DNA at a specific place, targeted by a guide RNA (gRNA).

 

This system is used by bacteria to fight off bacteriophages. Under normal circumstances, it transports the cut DNA to a region called CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, for storage. However, in genetic engineering, the cas9 enzyme and gRNA are used to spread an allele throughout a population.

 

Lab bred mosquitoes, carrying altered alleles, cas9 enzyme region, and gRNA, will be introduced into the wild. When this mosquito breeds with another mosquito, the cas9 enzyme region, guided by gRNA, will cut the offspring’s DNA at a specific place.

The individual cannot survive with damaged DNA, so the organism’s DNA repair system activates. The repair system will use the intact copy of the DNA, and fixes the cut region by copying the altered allele, cas9 enzyme, and the gRNA altogether.[6]

 

This means that the altered allele will be activated, but it also means that the allele will not disappear from nature. Alleles, through random mutation, change in frequency through a process called “genetic drift”; and genetic drift tends to make alleles disappear if they exist in small numbers. The cas9 system ensures that the altered allele exists throughout the population and proliferate.

 

This also means that whatever phenotypic effect the altered allele has will persist throughout the population. UCSD’s own Dr. Valentino Gantz shows how the allele works.[7] The altered allele codes for creation of antibodies in the mosquito’s immune system, designed to kill plasmodium malariae before it can infect a human. Not only that, it thickens a mosquito’s stomach so that plasmodium malariae will have a hard time escaping out of the mosquito’s stomach.

 

The implication of this system is groundbreaking. Not only will altered traits proceed to spread throughout the mosquito population, the cost incurred by conventional methods are eliminated. Unlike medicine, the CRISPR/cas9 system need not worry about parasite resistance, and unlike pesticides, the CRISPR/cas9 system only affects mosquitoes.

 

Although the CRISPR/cas9 system isn’t perfect, its possible role in the public health sector is imperative. Perhaps finally, humanity can swat away our unwelcome guests.

 

 

[1] https://www.mlsucsd.com/single-post/2019/02/10/Climate-Change-The-Sick-Reality

[2] https://en.wikipedia.org/wiki/Malaria#Life_cycle

[3] https://www.ecowatch.com/mosquito-spraying-ineffective-and-toxic-to-wildlife-and-humans-1881792509.html

[4] https://www.cdc.gov/malaria/malaria_worldwide/impact.html

[5] https://www.cdc.gov/malaria/malaria_worldwide/reduction/drug_resistance.html

[6] https://wyss.harvard.edu/media-post/crispr-cas9-gene-drives

[7] https://www.youtube.com/watch?v=J5WyEBTjJ38

 

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