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  • Writer's pictureNur Qiqi

The Magical Molecular Tool: CRISPR-Cas9

Edited by Season Wang.



Black hazy dots filled your vision as you slowly lost your eyesight. A pounding headache grew like a deafening roll of drums getting louder as you started to lose consciousness. You struggled but to no avail, fell into what felt like a pool of endless darkness. Your eyelids blanketed your cornea as you fainted on the ground.

Inside the cellular structure of your anatomy, a cell is wreaking havoc as it divides uncontrollably. It started off quiet, so hushed that even your immune system did not detect a single error. However, as time passed, the damaged cell multiplied, and as it grew larger in quantity, it started competing with the surrounding cells for nutrition. The cells around it begin to die as a result of malnutrition. The loud siren went off in your body, red lights flashing everywhere as your white blood cells worked tirelessly to fight the mutation.


Figure 1. Cancer cells undergoing mitosis

Though the stubborn cell was brilliant, it blocked your immune system and ignored every attack, continuing to grow into a group of mutated cells called tumours. As time passed, it became malignant as it metastasized to another part of your body inside your blood. It blocked nutrition, such as oxygen, from being transported to your brain, and as a result, your body fainted from oxygen deprivation.

Back into consciousness, you were struck with the most disturbing news that could happen to anyone. You have fallen victim to cancer.

According to the CDC (2022), the second leading cause of death in the United States is cancer.¹ The infamous disease has taken so many lives giving no regard to age, nationality, or gender. Everyone is at risk of developing cancer, and even with the new advancements in medicine and technology, not all death is preventable. Countless innocent lives were taken away, and there was almost nothing that the medical team could do to help. However, with the rising advancement of CRISPR technology, we might just find a tool that could help save more lives.


As technology is currently on the rise, it is essential for us to be aware and educated in this field. In this article, we will approach the complex and intricate system of CRISPR in a comprehensible manner.


Figure 2. CRISPR-Cas9 In Action

CRISPR-Cas9, pronounced as ‘crisper,’ stands for clustered regularly interspaced short palindromic repeat.² It sounds long and a bit of a mouthful, but it essentially is an editing tool for our genome.


Although the long name of CRISPR sounds intimidating, it was given deliberately to clearly describe its CRISPR molecular structure. Referring to the diagram, Paul Anderson explains that, “there will be short segments of DNA (up to 20 to 40 letters in length), where the segments are palindromic. A palindrome is a sequence of letters that read the same left-to-right. For instance, the sentence ‘never odd or even’ spells the same even if you read it backward. This particular DNA segment is known as the repeat.”³


Furthermore, the repeats are identical to each other, but they are interspaced (they have spaces between the repeat segments). This space is reserved for the spacers segments, which are non-identical to each other. They are arranged regularly and clustered together. The different spacers play a significant role in the mechanism of how CRISPR-Cas9 works.


What does CRISPR-Cas9 actually do? Well, think of a pair of scissors and glue that works on the molecular level. It enables us to remove, add or alter sections of our DNA sequence, which is the fundamental unit of life and where errors that cause diseases occur typically.⁴


Figure 3. How CRISPR-CAS9 works

Take cancers, for example. It is caused by a mutation in our DNA sequence that activates a proto-oncogene into an active oncogene – the gene responsible for a cell turning into a cancerous cell. Now, imagine if we are able to harness the power of technology fully. We could ‘deactivate’ the gene to turn it back into its proto-oncogenic state, which is completely harmless to the body.⁵ Yet, this is just the tip of the iceberg of what we can do with CRISPR-Cas9. If we manage to make use of the technology, a large door of endless possibilities will be opened. We could cure genetically-related diseases such as cancers, autoimmune diseases and even high cholesterol, HIV, and Huntington’s disease.⁶


A query might dance around in your mind, like, how did we even discover CRISPR-Cas9? It seems magical, almost unrealistic, how mere humans could alter their fundamental genome - the basic units that make us, us - using a molecular editor. Well, let us briefly dive into the history of how CRISPR-Cas9 was acknowledged by scientists.


Figure 4. E. coli bacteria

According to an article written by Ng D. (2020), “CRISPR-Cas9 was first identified in E. coli in 1987 by a Japanese scientist, Yoshizumi Ishino, and his team, who accidentally cloned an unusual series of repeated sequences interspersed with spacer sequences.”⁷ During the first discovery of CRISPR, the system was thought to be a novel DNA repair mechanism in thermophilic archaea and bacteria.⁸ Though, in early 2000, Mojica and coworkers noticed that the spacer sequences were similar to those found in bacteriophages, viruses, and plasmids. They discovered that viruses could not infect bacteria-harbouring homologous spacer sequences, suggesting that these sequences play a role in the adaptive immune system in prokaryotes - simple organisms like bacteria.


In simpler terms, CRISPR-Cas9 is an immune mechanism in prokaryotes that help them survive attacks from their nemesis, viruses. The spacers are identical to those sequences found in their opponent and are the ones that are responsible for the immunity of the prokaryote against its attackers. Think of Cas9 - a protein coloured grey in the diagram - as a gun, and spacers account for the specific bullet that is only effective against a specific opponent with a similar sequence to it. In the diagram shown, the bacteriophage can be seen injecting its sequence - coloured green - into the bacteria. The gun, aka Cas9 protein, was then immediately loaded with a specific bullet to counteract the attack.


Figure 5. Diagram showing the mechanism of CRISPR-Cas9

The complex and intricate way it counterattacks is the main reason why CRISPR was suggested to be used as a gene editor. It cleaves the complementary DNA or RNA viral sequences that just entered. In 2012, George Church, Jennifer Doudna, Emmanuelle Charpentier, and Feng Zhang discovered that by designing guide RNA - known as the spacers - to target a specific region in the genome, “the CRISPR-Cas9 system can be used as a ‘cut-and-paste’ tool to modify genomes.”⁷ This marked the breakthrough of the complex system and how it is continuously advancing to help humankind.


Nevertheless, we are still in the early days of CRISPR-Cas9 technology. As more applications are uncovered, the sky's the limit! In the future, we might even find a cure for cancers and genetic-related diseases. Many lives would be saved, and hopefully, soon, the advancement of CRISPR-Cas9 would come to fruition.


 

Reference:

  1. FastStats - Leading Causes of Death. (2022, January 13). CDC. Available at: https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm

  2. Moore, W. (2022, January 27). What Is CRISPR? WebMD. Available at: https://www.webmd.com/cancer/guide/crispr-facts-over (Moore, 2022)view

  3. What is CRISPR? (2016, February 18). YouTube. Available at: https://www.youtube.com/watch?v=MnYppmstxIs

  4. What is CRISPR-Cas9? – YourGenome. (2022, February 8). YourGenome. Available at: https://www.yourgenome.org/facts/what-is-crispr-cas9/

  5. Liu, P. (2022, July 29). ​Oncogene. NIH. Available at: https://www.genome.gov/genetics-glossary/Oncogene#:~:text=An%20oncogene%20is%20a%20mutated,in%20regulating%20normal%20cell%20division.

  6. Moore, W. (2022, January 27). What Is CRISPR? What Conditions Does It Treat? WebMD. Available at: https://www.webmd.com/cancer/guide/crispr-facts-overview

  7. Ng, D. (2020, June 30). A Brief History of CRISPR-Cas9 Genome-Editing Tools. Bitesize Bio. Available at: https://bitesizebio.com/47927/history-crispr/

  8. A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis. (n.d.). NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99818/







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