Eradicating Malaria with CRISPR Gene Drive

Malaria is no doubt one of the fatal diseases caused by different types of plasmodium species (Plasmodium falciparum, P. vivax, P. ovale, and P. malariae). It is no doubt a serious disease, and can be fatal. You see, one of the prevailing diseases in Africa is Malaria. As a child, I was also visiting the hospital, I guess it is due to my genotype, but I was always feasted upon by malaria. My mum was really worried and would always buy malaria medications for me as first aid before taking me to the hospital. You see, in my parent's house then, two things were always available which are anti-malaria medication, and insecticide. I still have insecticide in my house till date since malaria is nowhere near leaving. Malaria is actually being transmitted by a vector, which is the female Anopheles Mosquito. The Female Anopheles mosquito is also being infected by the parasite and, in the process of feeding, transmit it to humans. In this light, I have always looked forward to a day when we will have a Malaria free world.

Mosquitos are programmed to suck blood to survive and be able to reproduce, in our goal to conserve animals and save them from extinction, we would not decide to kill all mosquitoes, so we can be free from Malaria (not that we can kill them all, because 1 mosquito can lay up to 200 eggs), but then, what do you say about changing the genetic structure of the Female Anopheles mosquito, to become malaria resistant?

Malaria Statistics

In 2020, an estimate of 241 million case of malaria were reported and killed 627,000 people died of the disease worldwide. Sub-Saharan Africa mostly suffer from Malaria. While countries like the United States is a malaria free country, 2,000 cases of malaria are still being diagnosed yearly. This Malaria patients are immigrants from sub-Saharan Africa and South Asia. Children, within and below the age of 5 years, account for 80% of malaria death in Sub-Saharan and South Asian regions. In African, four countries account for over half of the total malaria death worldwide. These countries include Nigeria, Democratic Republic of the Congo, Tanzania, and Mozambique. Nigeria accounts for the largest with 31.9%, D.R.C with 13.2%, Tanzania with 4.1%, and Mozambique with 3.8%. In Nigeria, 76% of the population live in areas where malaria can be transmitted since most of its citizens live in areas close to swamp, bushes, or unkept regions with puddle, stagnant water and refuse dump.

Plasmodium/Malaria Life Cycle

In other, to understand Malaria, one needs to understand the plasmodium life cycle. The life cycle starts with a bite from the female Anopheles Mosquito. The Mosquito introduces the parasites (sporozoites) into the blood of the vertebrates (humans and animals) after being deposited in the dermis through it salivary gland. Immediately they get into the body, they head for the liver where they hide in Hepatocytes cell in the tissue of the liver where they multiply through a process known as Schizogony to become Merozoites. The Merozoite then find their way into the blood stream, invading every red blood cell (erythrocyte) they come across. In the red blood cell, the merozoites assexually multiply, thereby increasing the number of merozoites in the cell. Once they attack the red blood cell and reproduce, they go straight back into the blood and repeats reproduces every 72 hours in the case of P. malariae. These Merozoites develop into gametocyte for sexual reproduction.

Eliminating Malaria

Overtime, anti-malarial drugs have been given to patients with malaria but due to factors such as incomplete medications, the parasite start to resist the drugs and scientist need to keep producing more effective drugs. If we are to look back in time, drugs such as quinine have been used in the past, but this drug had effects on people such as irritation. With this, finding a solution to Malaria once and for all is the goal. Eliminating the parasite that kills human most is vital and to do this, scientists have started modifying the genetics of mosquitoes to prevent the spread of malaria. This is done via CRISPR Gene drive, and other CRISPR genetically modified methods. With Gene drive, endogenous sequences are targeted in mosquito's gene with the Cas9 nucleases and guide RNA which helps to target the insertion site in the DNA thereby allowing a copy. This has been done in A. gambiae and A. stephensi, to genetically create antibodies against malaria, as well as reduce the number of female malaria transferring mosquitoes by making them sterile. When the mosquitoes mate, they pass the gene to their offsprings. Gene drives are good, either the one that allows the mosquito gene to become resistant to malaria or the one that actually wants to shrink the number of female anopheles being reproduced by making them sterile. The goal, is to ensure the eradication of malaria.

Since each offspring receives a pair chromosome from each parent, then there is a 50% chance, for the genetically modified gene to be transferred, if the lab mosquitoes are released to the outside world. In the offspring, during Meiosis, the CRISPR gene would duplicate and modify the other chromosome, thereby allowing the spread of the modified chromosome to get to a large population. Since the lifespan of a mosquito is short, widespread will be within a short period of time (synthego).

Final Word

While Malaria vaccine is still being worked upon, using CRISPR technology to either eradicate mosquito by making the female infertile, or copy antibodies into their gene looks like a more suitable solution. Eradicating Malaria doesn't have to be expensive with CRISPR. Since it just requires editing the genetic composition of a few mosquitoes and allowing them to do the rest of the work. We haven't seen this being deployed in real world, but my worry now goes to Plasmodium mutation.

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Reference

• Center for disease control and prevention - What is malaria?

• Center for disease control and prevention - Malaria Faqs

• Whold Health Organization

• CDC.Gov - Life Cycle of Mosquito

• Nature.com - The silent path to thousands of merozoites: the Plasmodium liver stage

• ASM Journals - Mitosis in the Human Malaria Parasite Plasmodium falciparum

• Nature.com - Sexual development in Plasmodium parasites

• Malaria Journal - Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

• PNAS - Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi

• Nature Biotechnology - A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes

• Synthego - Eradicating Malaria with CRISPR: Mosquito Gene Editing Approach

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Images

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