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Biomedical Research Commentary

CRISPR Gene Editing: From novel treatment to reality

Originally released in the year 2000, the Marvel blockbuster film series features a team of six genetically enhanced beings called the X-Men. It appears that every time a new X-Men movie is released on the big screens, the world looks to science to answer the age-old question: “Is the creation of such mutants a possibility?”. 

With the endless developments in genetic engineering and the discovery of CRISPR-Cas9 gene editing in 2020, it is difficult not to wonder if the creation of such mutants in our reality is possible. Yet, much sooner than we expected, these so-called “superhumans” are already walking amongst us, with a range of unbelievable powers including super-strength, super-speed, and mind-blowingly high brain power that increasingly mirror superhuman powers seen on the big movie screens.

To understand the science behind these superhumans, we must first understand the basis of gene editing, which forms the foundation and function of CRISPR-Cas9.

What is CRISPR-Cas9?

CRISPR-Cas9 is a new and unique form of gene editing that allows medical scientists to edit parts of the genome by removing, adding, or altering sections of the DNA sequence [1]. Discovered back in 2021, it has been one of the frontiers of genomic research and a common hot topic within the medical community due to its simplicity, versatility, and precise method of genetic manipulation. The cheap price associated with CRISPR has ultimately made it more desirable than previous methods of DNA editing available on the market including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), which are much less cost-effective and accessible [2].

So why is CRISPR-Cas9 gene editing relevant to us right now?

The answer lies in the enormous potential of CRISPR gene editing for treating a wide range of life-threatening medical conditions that have a genetic basis and foundation such as cancer, hepatitis B, and high cholesterol. For example, the excess fatty deposits in major blood vessels causing high cholesterol can be resolved through genetic engineering techniques that “turn off” the genes that regulate cholesterol levels in our body [6]. A new study conducted by Nature 2021 revealed that knocking out the protein PCSK9 with CRISPR significantly reduced LDL cholesterol in monkeys by around 60% for at least 8 months [3]. Although it is likely to be many years before any testing for CRISPR technology can be carried out on humans, this kind of breakthrough within our own genus is impressive. As much current research is focused specifically on ex-vivo or animal models, the intention is to use the technology to routinely treat diseases in humans that can’t be addressed through routine drugs and medications.

How does this form of gene editing work?

The foundation of CRISPR-Cas9 is formed from two key molecules that introduce a mutation into the targeted DNA: the Cas9 enzyme and guide RNA (gRNA). The guide RNA has RNA bases that are complementary to the target DNA sequence in the original genome, and this helps the gRNA bind to the correct region within DNA. The Cas9 enzyme follows the gRNA and essentially acts as small scissors that make incisions within both strands of the DNA, allowing for sections of DNA to be added or removed [1][4]

At this point, the cell recognises the damage within the DNA and works to repair it, allowing scientists to use external machinery to introduce one or more new genes to the genome. This causes the genetic makeup to differ from the “normal” human genome, causing mutations and noticeable changes in the phenotype to occur such as the “super-variants” including super-sprinter variant (ACTN3), super-sleeper mutation (hDEC2), and the super-taster variant (TAS2R38) [5][7].

There is also extensive research being put into eliminating the “off-target” effects of CRISPR, where the Cas9 enzyme makes cuts at a site other than the intended one, introducing a mutation in the wrong region. Whilst some of these changes are inconsequential to the overall phenotype, they may affect the structure and function of another part of the genome. It is suggested that the use of Cas9 enzymes that only cut a single strand of target DNA as opposed to the double-strand may be the solution to eliminate this problem [4].

The next generation of enhanced individuals?

Though the alteration of the human genome is very much already a reality, the creation of ‘mutant’ individuals with more fantastical powers such as Wolverine’s special healing and animal keen senses, and the Scarlet Witch’s telekinesis and matter manipulation remains purely fictional. As of right now, the use of CRISPR in medicine is solely therapeutic, used for repairing or altering innate mutations, as opposed to creating them. Yet, it can be argued that these genetic changes allow the patient to have better DNA than the one they were born with, making them the first generation of genetically modified humans to walk the earth – mutants indeed.

In the X-Men franchise, all mutants carry an ‘X-gene’ which bestows upon them their aforementioned abilities. Unfortunately, no such gene exists – our phenotype arises from a much more complicated relationship between genes and presenting characteristics, and the effects of current gene editing pale in comparison to what is shown in blockbuster movies. That said, hope is not lost: extensive research and development within this field continually offer the possibility of giving individuals similar ‘powers’ to those of the X-Men and Professor X on an increasingly real scale. 

Below, are some examples of X-Men’s superpowers against their real-world human genetic mutation counterparts [5][7]:

X-Men abilityExisting human genetic variation
Animal-keen senseshDEC2 (super-sleeper mutation)  
Super-speedACTN3 (super-sprinter variant) 
Super-strengthLRP5 (unbreakable bone mutation)  
Enhanced sensesTAS2R38 (super-taster variant)  

Do scientists think it is possible for some of these powers to be attributed to genetic mutation? The simple answer is yes. But unsurprisingly, the uncertainty and unpredictable nature surrounding new treatments will always generate some degree of ethical controversy in the scientific community, and CRISPR is no different. The use of CRISPR technology in medicine will undoubtedly become more mainstream in the near future, and once the door is open for genetic modifications to embryos, babies, and adults alike, there is no going back. As with many medical technologies in the past, human health and safety may fail to be at the forefront of CRISPR’s use, leading to all kinds of unnecessary complications. The impact that CRISPR-Cas9 will have on the medical field, now and in the next generation, is undeniable – whether it’s curing a rare form of cancer or creating the first generation of real-life X-Men [8].

There are many unanswered questions surrounding this topic, and this is unlikely to change. But as the research continues and our questions go on, I would like to leave you with only one… What would your superpower be?

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Works Cited

1. Yourgenome.org. 2022. What is CRISPR-Cas9?. [online] Available at: https://www.yourgenome.org/facts/what-is-crispr-cas9 [Accessed 15 March 2022].

2. Beumer, K.J., Trautman, J.K., Christian, M., Dahlem, T.J., Lake, C.M., Hawley, R.S., Grunwald, D.J., Voytas, D.F. and Carroll, D. (2013). Comparing Zinc Finger Nucleases and Transcription Activator-Like Effector Nucleases for Gene Targeting in Drosophila. G3: Genes|Genomes|Genetics, [online] 3(10), pp.1717–1725. doi:10.1534/g3.113.007260.

3. Cen.acs.org. 2022. [online] Available at: https://cen.acs.org/pharmaceuticals/gene-therapy/One-time-CRISPR-hit-lowers-cholesterol-monkeys/99/i19 [Accessed 15 March 2022].

4. 2022. [online] Available at: https://futurism.com/crispr-genetic-engineering-change-world [Accessed 15 March 2022].

5. Business Insider. 2022. 8 genetic mutations that can give you ‘superpowers’. [online] Available at: https://www.businessinsider.com/genetic-mutations-that-make-you-more-awesome-2016-1 [Accessed 15 March 2022].

6. Newscientist.com. 2022. Gene tweak creates supermouse – and prevents diabetes | New Scientist. [online] Available at: https://www.newscientist.com/article/dn21156-gene-tweak-creates-supermouse-and-prevents-diabetes/ [Accessed 15 March 2022].

7. Business Insider. 2022. 8 genetic mutations that can give you ‘superpowers’. [online] Available at: https://www.businessinsider.in/science/8-genetic-mutations-that-can-give-you-superpowers/slidelist/50514398.cms#slideid=50514417 [Accessed 15 March 2022].

8. Pinkstone, J., 2022. Human beings could achieve immortality by 2050. [online] Mail Online. Available at: https://www.dailymail.co.uk/sciencetech/article-5408425/Human-beings-achieve￾immortality-2050.html [Accessed 15 March 2022].

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